Abstract
Objective
The treatment of breast cancer still faces great challenges, and it is
necessary to continuously explore effective drugs and targets to
promote immune precision medicine. This study aims to investigate the
immune-related regulatory mechanism of cordycepin in breast cancer.
Methods
Network pharmacology was employed to discovery the action of cordyceps
on breast cancer targets, molecular docking was employed to analyze the
interaction pattern between core components and targets, and biological
information analysis was used to explore the target-related immune
mechanism and verified in vitro experiments.
Results
The results of this study indicate that cordycepin can effectively
inhibit breast cancer. The roles of cordycepin's active component and
its target gene ALB were elucidated through the combined use of network
pharmacology and molecular docking. Bioinformatics analysis revealed
convincing associations between ALB and many immune pathway marker
genes. ALB was inhibited in tumor expression, and cordycepin was found
to enhance the expression of ALB in vitro to play an anti-tumor role.
Conclusion
Cordycepin regulates immune suppression of tumor, which is expected to
open a new chapter of breast cancer immunotherapy.
Keywords: Breast cancer, Immunotherapy, ALB, Cordycepin, Natural
medicines
1. Introduction
The number of new cases of breast cancer (BRCA) worldwide reached 2.26
million in 2020, and it has officially replaced lung cancer as the
first cancer in the world [[31]1]. In recent years, thanks to the
support of immunotherapy, the efficacy of BRCA has been significantly
improved [[32]2]. However, there is still a lot of room for improvement
in the treatment [[33]3]. The five-year survival rate of 90 % for BRCA
does not equal the cure rate, and advanced breast cancer is almost
incurable [[34]4](5). At present, the treatment methods have reached
the bottleneck, and it is urgent to find more effective therapies.
Immunotherapy is an innovation in the field of cancer treatment
[[35]5]. As a moderately or weakly immunogenic tumor with low mutation
burden, immunotherapy of breast cancer started late, but the
exploration in recent years is in full bloom [[36]6]. As a promising
treatment, immunotherapy has brought new hope to breast cancer
patients, especially those with triple-negative breast cancer [[37]7].
In recent years, a series of clinical studies on immunotherapy drugs
represented by immune checkpoint inhibitors have been carried out in
the field of breast cancer treatment, and breakthroughs have been made
[[38]8]. More immunotherapy drugs have been approved and the
accessibility of drugs has been improved.
The fruiting body of Cordyceps militaris (CM) holds significant
importance as a reservoir of natural products with diverse biological
activities. Widely recognized, it has been extensively employed both as
a crude drug and a functional food in various Asian regions [[39]9]. CM
has been associated with a range of reported pharmacological
activities, including antimicrobial, antifungal, antidiabetic,
anti-inflammatory, antiaging, and neuroprotective properties [[40]10].
In addition to the aforementioned activities, the extract from the
fruiting body of Cordyceps militaris (CME) demonstrates anticancer
effects against various cancer cell types, including ovarian, breast,
lung, colon, and skin cancers [[41]11](13). The principal active
constituent of CME responsible for its anticancer activity is
cordycepin, which is an analog of adenosine nucleoside [[42]12]. While
cordycepin demonstrates intriguing in vitro anticancer activity, its
limited application in clinical settings is often attributed to a lack
of specificity towards tumors. More investigation should be taken to
find the mechanism behind cordycepin and BRCA.
This study is expected to provide an important theoretical basis for
exploring the specific mechanism of cordycepin in the treatment of
BRCA, and provide new ideas for related immunotherapy.
2. Materials and methods
2.1. Network pharmacology analysis and molecular docking
2.1.1. Prediction of targets for cordycepin
First, search for the 2D and 3D structures of Cordycepin in the PubChem
database ([43]https://pubchem.ncbi.nlm.nih.gov/) [[44]13], and download
the corresponding SDF files containing both 2D and 3D structure
information. Then, upload the 3D structure file of Cordycepin to the
Pharm Mapper analysis platform
([45]http://www.lilab-ecust.cn/pharmmapper/) to predict its 71 targets
[[46]14].
2.1.2. Target screening for BRCA
Using the keyword “Breast Cancer”, search for disease-related targets
in the GeneCards database ([47]https://genealacart.genecards.org/) and
OMIM database ([48]https://www.omim.org/) [[49]15](18). Take the
results from both databases and take their union to obtain 17,006
BRCA-related targets.
2.1.3. Construction of regulatory network for cordycepin in BRCA
Use Perl software to map Cordycepin targets and BRCA disease targets
one-by-one, and obtain the intersection targets of Cordycepin and
diseases. Then, use Cytoscape software (V3.7.1) to perform network
visualization, obtaining a regulatory network of active
ingredients-intersection targets (see [50]Fig. 1). The types of nodes
include active ingredients and targets.
Fig. 1.
[51]Fig. 1
[52]Open in a new tab
Cordycepin Compounds- BRCA Targets.
The green circle was the active ingredient of cordycepin, and the red
diamond was the target.
(A)Venn diagram of cordycepin targets and BRCA targets (B) PPI network
of coincident Targets (C) The “Cordycepin Compounds- BRCA Targets”
network (D) Quantification of adjacent nodes of the key targets.
2.1.4. Construction of protein-protein interaction network (PPI) and core
target screening for intersection targets
Take the intersection targets of Cordycepin and BRCA-related targets as
the predicted targets of Cordycepin in BRCA treatment. Import the
predicted targets into the STRING online website, restricting the study
species to Homo sapiens and setting the others to default settings, to
obtain a PPI network [[53]16]. Draw a bar chart based on the number of
neighboring nodes of the targets.
2.1.5. Functional enrichment analysis
GO functional enrichment analysis mainly included three parts:
biological process (BP), cellular component (CC) and molecular function
(MF). The 62 intersection targets were processed using the Bioconductor
bioinformatics package in R language software to obtain GO functional
enrichment analysis and KEGG pathway enrichment analysis. Take p < 0.05
as statistically significant difference.
2.1.6. Molecular docking
Molecular docking primarily served for the structural docking of small
molecules to target proteins, enabling the evaluation of their binding
affinity to specific binding sites [[54]17]. A negative docking binding
energy signifies the effective autonomous binding of the small molecule
to the target protein. The general consensus is that the lower the
energy of conformational stabilization during ligand binding to the
receptor, the higher the likelihood of a significant effect. In this
study, we performed molecular docking of cordycepin and ALB (PDB ID:
[55]1N5U). The 3D structure map of hub targets was downloaded from
Protein Data Bank ([56]http://www.rcsb.org), saved in PDB format, and
imported into AutoDock software for molecular docking [[57]18]. PyMol
software was used to visualize the docking results.
2.1.7. Correlation analysis of ALB with immune pathway marker genes and
immune cell infiltration
We obtained a standardized dataset from the University of California,
Santa Cruz Genome Browser (UCSC) database
([58]https://xenabrowser.net/) [[59]19]. This dataset contained the
expression data of the ALB gene and 150 marker genes related to five
immune pathways, as well as 60 marker genes related to two immune
checkpoint pathways in each sample. The expression values were then
transformed using the log2 (x + 0.001) transformation. Subsequently, we
computed the Pearson correlation between ALB and immune pathway marker
genes. The Distribution of ALB expression across immune and molecular
subtypes was analyzed from the TISIDB database
([60]http://cis.hku.hk/TISIDB/browse.php) [[61]20]. Moreover, we
extracted tumor gene expression profiles and mapped them to GeneSymbol.
Additionally, we employed the TIMER
([62]https://cistrome.shinyapps.io/timer/) to ALB expression with
immune infiltration level in different BRCA subtypes [[63]21].
2.1.8. Differential expression of ALB in breast cancer
From the TCGA database ([64]https://portal.gdc.cancer.gov) to download
and organize TCGA - BRCA (breast ductal carcinoma) project STAR process
RNAseq data and extract the TPM format of the data, log2 (value + 1)
handles the data.
2.1.9. Cell culture and transient transfection
The human breast cancer cell lines MCF7 and MDA-MB-231, as well as the
human monocyte cell line THP-1, were procured from BNCC. MCF7 and
MDA-MB-231 cell lines were cultivated in DMEM F12 with 10 % FBS (Gibco,
Thermo Fisher, USA), while the THP-1 cell line was cultured in RPMI
medium 1640 with 10 % FBS (Gibco, Thermo Fisher, USA). Cultivation took
place at 37 °C in a humidified environment with 5 % CO2. Co-culturing
was facilitated using Transwell (Corning, USA).
2.1.10. Drug
The cell lines (2 × 10^4 cells/well) were subjected to treatment with
different concentrations of Cordycepin (10 μM, 20 μM, 50 μM, 100 μM, or
200 μM). Following an incubation period of 1 h, 12 h, and 24 h, the
cells were washed twice with PBS. Subsequently, CCK-8 (0.5 mg/mL in
PBS) was introduced to each well and incubated at 37 °C for 30 min.
2.1.11. Quantitative reverse transcription-polymerase chain reaction
(qRT-PCR)
Total RNA extraction was carried out using TRIzol reagent (Thermo
Fisher, USA). Subsequently, quantitative reverse
transcription-polymerase chain reaction (qRT-PCR) was conducted on the
extracted RNA from each sample (2 μg) using FastStart Universal SYBR
Green Master on a LightCycler 480 PCR System (Roche, USA). The cDNA
served as a template with a reaction volume of 20 μl (2 μl of cDNA
template, 10 μl of PCR mixture, 0.5 μl of forward and reverse primers,
and an appropriate volume of water). The PCR reactions were conducted
with the following cycling conditions: an initial DNA denaturation
phase at 95 °C for 30 s, followed by 45 cycles at 94 °C for 15 s, 56 °C
for 30 s, and 72 °C for 20 s. Each sample underwent three independent
analyses. Using the 2-ΔΔCT method, data from the threshold cycle (CT)
were obtained and normalized to the levels of GAPDH in each sample. The
mRNA expression levels were then compared to controls obtained from
normal tissues. Below is a list of primer pair sequences for the
targeted genes.
Gene Forward primer sequence (5′-3′) Reverse primer sequence (5′-3′)
SOD1 CTCACTCTCAGGAGACCATTGC CCACAAGCCAAACGACTTCCAG
CAT GTGCGGAGATTCAACACTGCCA CGGCAATGTTCTCACACAGACG
GPX4 ACAAGAACGGCTGCGTGGTGAA GCCACACACTTGTGGAGCTAGA
PRDX6 CAGCTACCACTGGCAGGAACTT GGAAGGACCATCACACTATCCC
IL6 AGACAGCCACTCACCTCTTCAG TTCTGCCAGTGCCTCTTTGCTG
TNF CTCTTCTGCCTGCTGCACTTTG ATGGGCTACAGGCTTGTCACTC
IL10 TCTCCGAGATGCCTTCAGCAGA TCAGACAAGGCTTGGCAACCCA
IL4 CCGTAACAGACATCTTTGCTGCC GAGTGTCCTTCTCATGGTGGCT
CD86 CCATCAGCTTGTCTGTTTCATTCC GCTGTAATCCAAGGAATGTGGTC
NOS2 GCTCTACACCTCCAATGTGACC CTGCCGAGATTTGAGCCTCATG
CD206 AGCCAACACCAGCTCCTCAAGA CAAAACGCTCGCGCATTGTCCA
ARG1 TCATCTGGGTGGATGCTCACAC GAGAATCCTGGCACATCGGGAA
GAPDH GTCTCCTCTGACTTCAACAGCG ACCACCCTGTTGCTGTAGCCAA
[65]Open in a new tab
2.1.12. ROS
In summary, cells were cultured in 6-well plates and treated as per
experimental groups. Following medium removal, 10 μmol/L DCFH-DA
(Beyotime, China) in 1 mL was added to each well, and incubation ensued
for 20 min. Subsequently, cells were washed with serum-free medium to
eliminate unabsorbed DCFH-DA. After sealing, fluorescence microscopy
was employed to observe green color intensity (excitation wavelength:
485 nm, emission wavelength: 530 nm). ImageJ software analyzed the
observed fluorescence to indicate cellular oxidation levels. Data were
processed using GraphPad Prism 8.0 (version 8.0, GraphPad Software, La
Jolla, CA, USA), and statistical significance was determined at
p < 0.05.
2.1.13. Cell culture and transient transfection
Human breast cancer cell lines MCF7 and MDA-MB-231 and human monocyte
cell line THP-1 were purchased from BNCC. MCF7 and MDA-MB-231 cell
lines were cultured in DMEM F12 with 10 % FBS (Gibco, Thermo Fisher,
USA). THP-1 cell line was cultured in RPMI medium 1640 with 10 % FBS
(Gibco, Thermo Fisher, USA). Cells were grown at 37 °C in a humidified
environment containing 5 % CO2. Transwell (Corning, USA) was used to
co-culture. The target sequences of small interfering RNA are listed.
Taeget target sequence (5′-3′)
si-ALB#1 GTCCATTTGAAGATCATGTAAAA
si-ALB#2 AAGATCATGTAAAATTAGTGAAT
[66]Open in a new tab
2.1.14. 5-Ethynyl-2′-deoxyuridine (EdU) assay
EdU assay was performed using BeyoClick™ EdU Cell Proliferation Kit
containing Alexa Fluor 594 (Boyetime, Shanghai, China). After rinsing
with PBS, cells were incubated with EdU solution for 2 h and then
stained with DAPI solution for nuclei. After washing, the samples were
observed with an inverted microscope (Olympus).
3. Results
3.1. Construction of “Cordycepin Compounds- BRCA targets” network
A total of 62 overlapping targets were included after comparivng
cordycepin targets and BRCA targets ([67]Fig. 1A), and the cordycepin
targets and BRCA targets were mapped one by one. The “Cordycepin
Compounds- BRCA Targets” network was constructed, as the degree values
of nodes were calculated in Cytoscape 3.7.2 ([68]Fig. 1B).
3.2. Construction of a protein-protein interaction (PPI) network of targets
A PPI network was constructed after 62 targets were uploaded to the
STRING database ([69]Fig. 1C). According to the number of adjacent
nodes of the key targets, ALB, PGK1, EIF5A, ACO1, IGF1R, OLA1, RRM1,
CDKN1B, PA2G4 and UBE3A were located in the core of the network, which
might be the core genes of cordycepin against BRCA, and ALB was the
most important one ([70]Fig. 1D).
3.3. Analysis of GO pathway and KEGG pathway
GO functional enrichment analysis and KEGG pathway enrichment analysis
were carried out using the Bioconductor bioinformatics package in R
language software. With p < 0.05 as the screening condition, in GO
functional enrichment analysis, the top three biological processes that
were significantly enriched by BP included: protein tetramerization,
regulation of protein complex disassembly and somatic diversification
of immunoglobulins. The top three cellular components that were
significantly enriched by CC included: secretory granule lumen,
cytoplasmic vesicle lumen, and vesicle lumen. The top 10 molecular
functions with obvious MF enrichment included: core promoter
sequence-specific DNA binding, insulin receptor substrate binding, and
insulin-like growth factor I binding ([71]Fig. 2A–B). In KEGG pathway
enrichment analysis, the top three pathways are protein
tetramerization, regulation of protein complex disassembly, and somatic
diversification of immunoglobulins ([72]Fig. 2C–D).
Fig. 2.
[73]Fig. 2
[74]Open in a new tab
Diagram for GO and KEGG enrichment analysis.
The bubble size represents the number of enriched genes, and the bubble
color difference represents the significant magnitude of target gene
enrichment.
(A)Molecular Function enrichment analysis (B)Cellular Component
enrichment analysis (C) Biological Process enrichment analysis (D) KEGG
functional enrichment analysis.
3.4. Molecular docking of the binding interaction between cordycepin and ALB
Through network pharmacology analysis and molecular docking, we
discovered that cordycepin can bind to ALB through hydrogen bonding and
strong electrostatic interactions, indicating a highly stable binding
([75]Fig. 3A–B). The molecular formula of cordycepin was shown in
[76]Fig. 3C.
Fig. 3.
[77]Fig. 3
[78]Open in a new tab
Molecular docking of the binding interaction between cordycepin and
ALB.
(A,B) The molecular docking of cordycepin and ALB, where the blue box
portion is magnified, shows the interaction of additional residues and
hydrogen bonds. The blue structure indicates the binding site of ALB
protein to cordycepin, the yellow hydrogen bond, and the bond energy is
labeled next to it. (C) Chemical structure diagram of cordycepin.
3.5. ALB with immune pathway marker genes and immune cell infiltration in
different BRCA subtypes
Subsequently, we performed bioinformatics analysis to investigate the
regulatory effects of ALB on immune modulatory genes and immune
infiltration in different BRCA subtypes, and its expression is
relatively low in tumors ([79]Fig. 4A–C). ALB showed a significant
association with immune infiltration scores of B cells in BRCA, CD8^+ T
cells in BRCA-Luminal ([80]Fig. 4D). Furthermore, The results revealed
significant correlations between ALB and multiple immune pathway
markers ([81]Fig. 4E).
Fig. 4.
[82]Fig. 4
[83]Open in a new tab
The regulatory effects of the ALB gene on immune modulatory genes and
immune infiltration in different BRCA subtypes.
Analysis of the infiltration scores of B cells, CD8^+ T cells, CD4^+ T
cell, macrophages, neutrophils, and dendritic cells based on the
expression levels of ALB in patients. (B) Associations between ALB
expression and immune subtypes across breast cancer. (C) Associations
between ALB expression and molecular subtypes across breast cancer. (D)
A comparison was performed between the ALB gene and 60 genes associated
with two categories of immune checkpoint pathways to assess their
correlation. * represents p < 0.05, ** represents p < 0.001, ***
represents p < 0.0001.
3.6. Cordycepin is effective in treating human breast cancer cell lines in
vitro
We performed experimental treatment of human breast cancer cell lines
MCF7 and MDA-MB-231 in vitro with five concentrations of cordycepin,
10 μM, 20 μM, 50 μM, 100 μM or 200 μM. The viability of human breast
cancer cell lines decreased rapidly with increasing concentrations of
cordycepin, but the three therapeutic concentrations of 50 μM, 100 μM
or 200 μM had the same inhibitory ability for human breast cancer cell
lines ([84]Fig. 5A–B). We then examined changes in the transcript
levels of ALB in human breast cancer cell lines after cordycepin
treatment. In contrast to the tendency of rapid decrease in cell
viability, the transcript levels of ALB in human breast cancer cell
lines increased rapidly after cordycepin treatment until 50 μM after
which there was no further change ([85]Fig. 5C–D). For this reason, we
selected 50 μM cordycepin as the therapeutic concentration in vitro.
Elevated reactive oxygen species (ROS) lead to apoptosis, and for this
reason we examined the levels of ROS in human breast cancer cell lines
after cordycepin treatment. We observed a rapid increase in ROS levels
in cordycepin-treated human breast cancer cell lines, suggesting that a
response to cordycepin treatment exists in human breast cancer cell
lines ([86]Fig. 5E–F). Given this finding, we examined the activity of
ROS clearance enzymes in human breast cancer cell lines before and
after cordycepin treatment. Transcript levels of SOD1, CAT, GPX4, and
PRDX6 decreased rapidly after cordycepin treatment, indicating a rapid
decrease in ROS scavenging capacity in human breast cancer cell lines
after cordycepin treatment. Meanwhile elevated ROS levels in human
breast cancer cell lines were also accompanied by elevated
transcription of pro-inflammatory cytokines, such as IL6 and TNF. At
the same time, the transcription of anti-inflammatory cytokines, such
as IL4 and IL10, was significantly decreased ([87]Fig. 5G). Macrophage
polarization may have a different role for tumor progression, and for
this reason we examined the phenotype of THP-1 cells after co-culture
of human breast cancer cell lines before and after treatment with
cordycepin. Upon co-culture with cordycepin-treated human breast cancer
cell lines, the transcription of CD86 and NOS2 in THP-1 was enhanced,
reflecting the tendency of M1 polarization. Meanwhile, the
transcription of CD206 and ARG1 in THP-1 was significantly inhibited,
exhibiting suppression of M2 polarization ([88]Fig. 5I–M). Firstly, we
observed the effect of cordycepin in direct treatment of breast cancer
cell lines.The results of CCK8 suggested that cordycepin had a slight
inhibitory effect on MCF7 and MDA-MB-231, but not as significant as
co-culture with THP-1 ([89]Fig. 6 C-D). To clarify the effect of ALB on
breast cancer cell lines, we used small interfering RNA to inhibit ALB
expression in breast cancer cell lines. The results of EdU staining
suggested that the proliferative capacity of MCF7 and MDA-MB-231 cell
lines was significantly increased after ALB knockdown, which was
similarly corroborated by the results of CCK8 ([90]Fig. 6 E-F). THP-1
after cordycepin stimulation no longer exhibits strong inhibitory
effects on breast cancer cell lines with knocked-down ALB ([91]Fig. 6).
Fig. 5.
[92]Fig. 5
[93]Open in a new tab
Cordycepin is effective in treating human breast cancer cell lines in
vitro.
(A–B) Changes in cell viability of MCF7 and MDA-MB-231 cell lines after
treatment with different concentrations of cordycepin and relative
quantitative analysis. (C–D) Transcriptional alterations of ALB in MCF7
and MDA-MB-231 cell lines after treatment with different concentrations
of cordycepin and relative quantitative analysis. (E–F) Changes in ROS
intensity in MCF7 and MDA-MB-231 cell lines after cordycepin treatment
and quantitative analysis of mean fluorescence intensity. (G)
Transcriptional changes of inflammatory cytokines in cordycepin-treated
human breast cancer cell lines with relative quantitative analysis. (I)
Schematic representation of human breast cancer cell lines co-cultured
with THP-1 cell line before and after cordycepin treatment. (J–M)
Changes in transcript levels of M1/M2 makers in THP-1 cell lines
co-cultured with human breast cancer cell lines before and after
cordycepin treatment. n = 3. *
[MATH: < :MATH]
0.05, **
[MATH: < :MATH]
0.01, ***
[MATH: < :MATH]
0.001, ****
[MATH: < :MATH]
0.0001. The results are presented as mean ± SEM.
Fig. 6.
[94]Fig. 6
[95]Open in a new tab
ALB inhibits the proliferative capacity of breast cancer cell lines.
(A–B) Representative EdU staining results of MCF-7 and MDA-MB-231 cell
lines before and after ALB inhibition. (C–D) CCK8 results of MCF-7 and
MDA-MB-231 cell lines before and after cordycepin treatment and
relative quantitative analysis. (E–F) CCK8 results of MCF-7 and
MDA-MB-231 cell lines co-cultured with cordycepin-treated THP-1 before
and after inhibition of ALB and analyzed for relative quantification.
(G–H) CCK8 results of MCF-7 and MDA-MB-231 cell lines before and after
ALB inhibition and relative quantitative analysis.
4. Discussion
At present, the research on the anticancer effect of cordycepin has
progressed rapidly, and more and more mechanisms have been discovered
[[96]22]. Cordycepin possesses a number of pharmacological functions
including anti-cancer effect, anti-inflammatory and neuroprotective
effects [[97]23](27). However, its detailed anticancer mechanisms in
breast cancer are still not clear.
Cordycepin can play the role of bidirectional immune regulation by
improving cellular immune function, inhibiting the production of IL-2
by plant hemagglutinins and the expansion of monocytes in peripheral
blood [[98]24]. Anti-il-10 neutral antibody could not completely block
the inhibitory effect of cordycepin on IL-2 production. Under the
action of cordycepin, mature dendritic cells can induce the
proliferation of regulatory T cells, inhibit cell division, promote
cell differentiation, change the structure and distribution of
substances on the cell membrane, and promote the transformation of T
lymphocytes [[99]25]. It can also improve the phagocytic function of
the body's monocyte-macrophage system, activate macrophages to produce
cytotoxins and directly kill cancer cells. Cordycepin resulted in
enhanced transcription of CD86 and NOS2 in THP-1 cells, reflecting the
trend towards M1 polarization. At the same time, the transcription of
CD206 and ARG1 in THP-1 cells was significantly inhibited, which was
manifested as the inhibition of M2 polarization. Human total ALB pool
is affected by ALB gene expression and ALB catabolism [[100]26]. The
gene ALB has previously been observed to contribute to the metabolic
reprogramming of HCC(31). In different pathophysiological states, ALB
can stimulate or alleviate immune cell activation [[101]27]. The main
way is to stimulate the intrinsic immune cells such as neutrophils,
macrophages and vascular endothelial cells through specific receptors
to induce various inflammatory mediators, including cytokines,
arachidonic acids, prostaglandins, thromboxins, leukotrienes and
various ROS and RNS substances [[102]28](34). Its expression is low in
breast tumors and stable and consistent in different subtypes and
different periods, suggesting that it may be a potential therapeutic
target.
Although cordycepin has shown promising experimental results in
inhibiting breast cancer, there are still many challenges. The high
production cost of cordycepin makes it relatively expensive, limiting
its wide clinical use. There are still many ways to go in the clinical
application of Chinese medicine. In the clinical application of Chinese
medicine, it is necessary to strengthen the quality control, in-depth
study of its pharmacological mechanism, establish a scientific
evaluation system, and combine clinical practice experience to select
and apply Chinese medicine reasonably. The efficacy of single drug is
limited, and drugs with multiple mechanisms of action are urgently
needed to improve the efficacy, including immune combined with
chemotherapy, dual immune combination, and immune combined with
targeted therapy. How to explore the best combination regimen and find
biomarkers of benefit are still unclear. How to further improve the
efficacy of immunotherapy is the key to its clinical application in the
future. In clinical application, it is necessary to weigh its
advantages and disadvantages, and make reasonable decisions based on
specific conditions and patient conditions. Cordycepin regulates immune
suppression of tumor, which is expected to open a new chapter of breast
cancer immunotherapy.
Cordycepin, as a natural source of anti-tumor active ingredient, Safety
is high. Our finding that cordycepin can enhance anti-tumor immunity in
breast cancer by enhanceing ALB expressio This may provide a
theoretical basis for the application of cordycepin derivatives in the
treatment of breast cancer. Cordycepin can be used as an adjuvant drug
to improve the efficacy of anti-tumor drugs, which provides new ideas
and theoretical basis for the development of anticancer drugs in the
future.
Consent for publication
All the authors provided written informed consent for the publication
of the manuscript.
Funding
There was no fund support.
Availability of data and material
Cordycepin related data are available in the public repository.
Contributors
All contributors are listed as authors.
CRediT authorship contribution statement
Lin Chen: Writing – review & editing, Writing – original draft,
Visualization, Software, Methodology, Formal analysis, Data curation,
Conceptualization. Weihao Wei: Writing – original draft, Visualization,
Validation, Data curation, Conceptualization. Jin Sun: Writing –
original draft, Validation, Supervision, Software, Methodology,
Conceptualization. Beicheng Sun: Writing – review & editing,
Validation, Supervision, Methodology, Conceptualization. Rong Deng:
Writing – review & editing, Visualization, Validation, Supervision,
Conceptualization.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to
influence the work reported in this paper.
Acknowledgements