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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
ISSN (Online): 1875-5402

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Research Article

Study on the Mechanism of Astragalus Polysaccharides on Cervical Cancer Based on Network Pharmacology

Author(s): Wen-Zhi Liu, Min-Min Yu* and Min Kang

Volume 26, Issue 8, 2023

Published on: 03 February, 2023

Page: [1547 - 1559] Pages: 13

DOI: 10.2174/1386207326666230118121436

Price: $65

Abstract

Background: Astragalus polysaccharides (APS) is a natural phytochemical which has been extensively utilized for anti-tumor therapy over the past few years. However, its impact on cervical cancer (CC) has rarely been studied.

Objective: To clarify the exact mechanism of anti-cancer effects of Astragalus polysaccharides (APS) on Cervical Cancer (CC), we screened differentially expressed genes (DEGs) from The Cancer Genome Atlas (TCGA) to construct the cancer network.

Methods: Then we performed functional enrichment analysis with gene ontology (GO) and KEGG pathway analyses, constructed protein-protein interaction (PPI) network, and performed molecular docking (MD) analysis to identify the key gene for docking with APS. Further, we observed the effects of APS on cell proliferation, cell cycle, and apoptosis experiments in HeLa cells. qRT-PCR and western blot were used to detect the expression of target genes.

Results: A total of 793 DEGs were screened using criteria, which included 541 genes that were upregulated and 251 genes that were down-regulated. Using topological attributes for identifying critical targets, molecular docking (MD), and survival analyses, this study predicted the APS targets: POLO-like kinase 1(PLK1), Cyclin-cell division 20(CDC20), and Cyclin-dependent kinase 1 (CDK1), which regulated HeLa cells. The results of cell proliferation, cell cycle, and apoptosis experiments concluded that APS inhibited the development of HeLa cells in a concentrationdependent manner. Also, qRT-PCR and western blot experiments demonstrated that APS could significantly down-regulate the expression of PLK1, CDC20, and CDK1 in the CC cells.

Conclusion: The result revealed that APS might have a therapeutic potential in treating CC and might permit intervention with treatments targeting PLK1, CDC20, and CDK1.

Keywords: Astragalus polysaccharides, cervical cancer, network pharmacology, TCGA, PLK1, CDC20, CDK1.

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[1]
Edathara, P.M.; Chintalapally, S.; Makani, V.K.K.; Pant, C.; Yerramsetty, S.D.; Rao, M.; Bhadra, M.P. Inhibitory role of oleanolic acid and esculetin in HeLa cells involve multiple signaling pathways. Gene, 2021, 771, 145370.
[http://dx.doi.org/10.1016/j.gene.2020.145370] [PMID: 33346097]
[2]
Arbyn, M.; Weiderpass, E.; Bruni, L.; de Sanjosé, S.; Saraiya, M.; Ferlay, J.; Bray, F. Estimates of incidence and mortality of cervical cancer in 2018: A worldwide analysis. Lancet Glob. Health, 2020, 8(2), e191-e203.
[http://dx.doi.org/10.1016/S2214-109X(19)30482-6] [PMID: 31812369]
[3]
Revathidevi, S.; Murugan, A.K.; Nakaoka, H.; Inoue, I.; Munirajan, A.K. APOBEC: A molecular driver in cervical cancer pathogenesis. Cancer Lett., 2021, 496, 104-116.
[http://dx.doi.org/10.1016/j.canlet.2020.10.004] [PMID: 33038491]
[4]
Golfetto, L.; Alves, E.V.; Martins, T.R.; Sincero, T.C.M.; Castro, J.B.S.; Dannebrock, C.; Oliveira, J.G.; Levi, J.E.; Onofre, A.S.C.; Bazzo, M.L. PCR-RFLP assay as an option for primary HPV test. Braz. J. Med. Biol. Res., 2018, 51(5), e7098.
[http://dx.doi.org/10.1590/1414-431x20177098] [PMID: 29590262]
[5]
Lanza, A.; Tava, A.; Catalano, M.; Ragona, L.; Singuaroli, I.; Robustelli della Cuna, F.S.; Robustelli della Cuna, G. Effects of the medicago scutellata trypsin inhibitor (MsTI) on cisplatin-induced cytotoxicity in human breast and cervical cancer cells. Anticancer Res., 2004, 24(1), 227-233.
[PMID: 15015601]
[6]
Park, S.H.; Kim, M.; Lee, S.; Jung, W.; Kim, B. Therapeutic potential of natural products in treatment of cervical cancer: A review. Nutrients, 2021, 13(1), 154.
[http://dx.doi.org/10.3390/nu13010154] [PMID: 33466408]
[7]
Li, K.; Cui, L.J.; Cao, Y.X.; Li, S.Y.; Shi, L.X.; Qin, X.M.; Du, Y.G. UHPLC Q-exactive MS-based serum metabolomics to explore the effect mechanisms of immunological activity of Astragalus polysaccharides with different molecular weights. Front. Pharmacol., 2020, 11, 595692.
[http://dx.doi.org/10.3389/fphar.2020.595692] [PMID: 33390982]
[8]
Guo, Y.; Zhang, Z.; Wang, Z.; Liu, G.; Liu, Y.; Wang, H. Astragalus polysaccharides inhibit ovarian cancer cell growth via microRNA-27a/FBXW7 signaling pathway. Biosci. Rep., 2020, 40(3), BSR20193396.
[http://dx.doi.org/10.1042/BSR20193396] [PMID: 32159214]
[9]
Bamodu, O.A.; Kuo, K.T.; Wang, C.H.; Huang, W.C.; Wu, A.T.H.; Tsai, J.T.; Lee, K.Y.; Yeh, C.T.; Wang, L.S. Astragalus polysaccharides (PG2) enhances the M1 polarization of macrophages, functional maturation of dendritic cells, and T cell-mediated anticancer immune responses in patients with lung cancer. Nutrients, 2019, 11(10), 2264.
[http://dx.doi.org/10.3390/nu11102264] [PMID: 31547048]
[10]
Huang, W.C.; Kuo, K.T.; Bamodu, O.A.; Lin, Y.K.; Wang, C.H.; Lee, K.Y.; Wang, L.S.; Yeh, C.T.; Tsai, J.T. Astragalus polysaccharide (PG2) ameliorates cancer symptom clusters, as well as improves quality of life in patients with metastatic disease, through modulation of the inflammatory cascade. Cancers (Basel), 2019, 11(8), 1054.
[http://dx.doi.org/10.3390/cancers11081054] [PMID: 31349728]
[11]
Bao, W.R.; Li, Z.P.; Zhang, Q.W.; Li, L.F.; Liu, H.B.; Ma, D.L.; Leung, C.H.; Lu, A.P.; Bian, Z.X.; Han, Q.B. Astragalus polysaccharide RAP selectively attenuates paclitaxel-induced cytotoxicity toward RAW 264.7 cells by reversing cell cycle arrest and apoptosis. Front. Pharmacol., 2019, 9, 1580.
[http://dx.doi.org/10.3389/fphar.2018.01580] [PMID: 30804792]
[12]
Wu, C.Y.; Ke, Y.; Zeng, Y.F.; Zhang, Y.W.; Yu, H.J. Anticancer activity of Astragalus polysaccharide in human non-small cell lung cancer cells. Cancer Cell Int., 2017, 17(1), 115.
[http://dx.doi.org/10.1186/s12935-017-0487-6] [PMID: 29225515]
[13]
Zhao, X.; Du, S.; Chai, L.; Xu, Y.; Liu, L.; Zhou, X.; Wang, J.; Zhang, W.; Liu, C.; Wang, X. Anti-cancer drug screening based on an adipose-derived stem cell/hepatocyte 3D printing technique. J. Stem Cell Res. Ther., 2015, 5, 273.
[14]
Li, C.; Hong, L.; Liu, C.; Min, J.; Hu, M.; Guo, W. Astragalus polysaccharides increase the sensitivity of SKOV3 cells to cisplatin. Arch. Gynecol. Obstet., 2018, 297(2), 381-386.
[http://dx.doi.org/10.1007/s00404-017-4580-9] [PMID: 29103194]
[15]
Tan, Y.; Yin, L.; Sun, Z.; Shao, S.; Chen, W.; Man, X.; Du, Y.; Chen, Y. Astragalus polysaccharide exerts anti-Parkinson via activating the PI3K/AKT/mTOR pathway to increase cellular autophagy level in vitro. Int. J. Biol. Macromol., 2020, 153, 349-356.
[http://dx.doi.org/10.1016/j.ijbiomac.2020.02.282] [PMID: 32112840]
[16]
Wang, X.; Li, Y.; Liu, D.; Wang, Y.; Ming, H. Astragalus polysaccharide inhibits autophagy and regulates expression of autophagy-related proteins in lung cancer A549 cells induced by xanthine oxidase. Xibao Yu Fenzi Mianyixue Zazhi, 2019, 35(7), 619-624.
[PMID: 31537247]
[17]
Wu, J.; Wang, J.; Su, Q.; Ding, W.; Li, T.; Yu, J.; Cao, B. Traditional Chinese medicine Astragalus polysaccharide enhanced antitumor effects of the angiogenesis inhibitor apatinib in pancreatic cancer cells on proliferation, invasiveness, and apoptosis. OncoTargets Ther., 2018, 11, 2685-2698.
[http://dx.doi.org/10.2147/OTT.S157129] [PMID: 29785118]
[18]
Wu, J.; Yu, J.; Wang, J.; Zhang, C.; Shang, K.; Yao, X.; Cao, B. Astragalus polysaccharide enhanced antitumor effects of Apatinib in gastric cancer AGS cells by inhibiting AKT signalling pathway. Biomed. Pharmacother., 2018, 100, 176-183.
[http://dx.doi.org/10.1016/j.biopha.2018.01.140] [PMID: 29428665]
[19]
Zhou, Y.; Hong, T.; Tong, L.; Liu, W.; Yang, X.; Luo, J.; Wang, F.; Li, J.; Yan, L. Astragalus polysaccharide combined with 10-hydroxycamptothecin inhibits metastasis in non-small cell lung carcinoma cell lines via the MAP4K3/mTOR signaling pathway. Int. J. Mol. Med., 2018, 42(6), 3093-3104.
[http://dx.doi.org/10.3892/ijmm.2018.3868] [PMID: 30221690]
[20]
Meng, Q.; Du, X.; Wang, H.; Gu, H.; Zhan, J.; Zhou, Z. Astragalus polysaccharides inhibits cell growth and pro-inflammatory response in IL-1β-stimulated fibroblast-like synoviocytes by enhancement of autophagy via PI3K/AKT/mTOR inhibition. Apoptosis, 2017, 22(9), 1138-1146.
[http://dx.doi.org/10.1007/s10495-017-1387-x] [PMID: 28660311]
[21]
Zhai, Q.L.; Hu, X.D.; Xiao, J.; Yu, D.Q. Astragalus polysaccharide may increase sensitivity of cervical cancer HeLa cells to cisplatin by regulating cell autophagy. Zhongguo Zhongyao Zazhi, 2018, 43(4), 805-812.
[PMID: 29600659]
[22]
Lai, X.; Xia, W.; Wei, J.; Ding, X. Therapeutic effect of astragalus polysaccharides on hepatocellular carcinoma H22-bearing mice. Dose Response, 2017, 15(1)
[http://dx.doi.org/10.1177/1559325816685182] [PMID: 28210201]
[23]
Hopkins, A.L. Network pharmacology. Nat. Biotechnol., 2007, 25(10), 1110-1111.
[http://dx.doi.org/10.1038/nbt1007-1110] [PMID: 17921993]
[24]
Li, S. Exploring traditional chinese medicine by a novel therapeutic concept of network target. Chin. J. Integr. Med., 2016, 22(9), 647-652.
[http://dx.doi.org/10.1007/s11655-016-2499-9] [PMID: 27145941]
[25]
Wang, X.; Wang, Z.Y.; Zheng, J.H.; Li, S. TCM network pharmacology: A new trend towards combining computational, experimental and clinical approaches. Chin. J. Nat. Med., 2021, 19(1), 1-11.
[http://dx.doi.org/10.1016/S1875-5364(21)60001-8] [PMID: 33516447]
[26]
Wu, X.M.; Wu, C.F. Network pharmacology: A new approach to unveiling traditional Chinese medicine. Chin. J. Nat. Med., 2015, 13(1), 1-2.
[http://dx.doi.org/10.1016/S1875-5364(15)60001-2] [PMID: 25660283]
[27]
Tang, J.; Aittokallio, T. Network pharmacology strategies toward multi-target anticancer therapies: from computational models to experimental design principles. Curr. Pharm. Des., 2014, 20(1), 23-36.
[http://dx.doi.org/10.2174/13816128113199990470] [PMID: 23530504]
[28]
Jiao, X.; Sherman, B.T.; Huang, D.W.; Stephens, R.; Baseler, M.W.; Lane, H.C.; Lempicki, R.A. DAVID-WS: A stateful web service to facilitate gene/protein list analysis. Bioinformatics, 2012, 28(13), 1805-1806.
[http://dx.doi.org/10.1093/bioinformatics/bts251] [PMID: 22543366]
[29]
Huang, D.W.; Sherman, B.T.; Lempicki, R.A. Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat. Protoc., 2009, 4(1), 44-57.
[http://dx.doi.org/10.1038/nprot.2008.211] [PMID: 19131956]
[30]
Szklarczyk, D.; Morris, J.H.; Cook, H.; Kuhn, M.; Wyder, S.; Simonovic, M.; Santos, A.; Doncheva, N.T.; Roth, A.; Bork, P. The STRING database in 2017: Quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res., 2017, 45(D1), D362-D368.
[PMID: 27924014]
[31]
Su, G.; Morris, J.H.; Demchak, B.; Bader, G.D. Biological network exploration with cytoscape 3. Curr. Protoc. Bioinformatics, 2014, 47(1), 13.1-24.
[http://dx.doi.org/10.1002/0471250953.bi0813s47]] [PMID: 25199793]
[32]
Wang, M.; Liao, J.; Wang, J.; Qi, M.; Wang, K.; Wu, W. TAF1A and ZBTB41 serve as novel key genes in cervical cancer identified by integrated approaches. Cancer Gene Ther., 2021, 28(12), 1298-1311.
[PMID: 33311601]
[33]
D’Souza, L.C.; Mishra, S.; Chakraborty, A.; Shekher, A.; Sharma, A.; Gupta, S.C. Oxidative stress and cancer development: Are noncoding RNAs the missing links? Antioxid. Redox Signal., 2020, 33(17), 1209-1229.
[http://dx.doi.org/10.1089/ars.2019.7987] [PMID: 31891666]
[34]
Hu, J.X.; Thomas, C.E.; Brunak, S. Network biology concepts in complex disease comorbidities. Nat. Rev. Genet., 2016, 17(10), 615-629.
[http://dx.doi.org/10.1038/nrg.2016.87] [PMID: 27498692]
[35]
Zhang, A.; Sun, H.; Wang, P.; Han, Y.; Wang, X. Future perspectives of personalized medicine in traditional Chinese medicine: A systems biology approach. Complement. Ther. Med., 2012, 20(1-2), 93-99.
[http://dx.doi.org/10.1016/j.ctim.2011.10.007] [PMID: 22305254]
[36]
Zhang, C.; Zhou, W.; Guan, D.G.; Wang, Y.H.; Lu, A.P. Network intervention, a method to address complex therapeutic strategies. Front. Pharmacol., 2018, 9, 754.
[http://dx.doi.org/10.3389/fphar.2018.00754] [PMID: 30050441]
[37]
Lyu, M.; Yan, C.L.; Liu, H.X.; Wang, T.Y.; Shi, X.H.; Liu, J.P.; Orgah, J.; Fan, G.W.; Han, J.H.; Wang, X.Y.; Zhu, Y. Network pharmacology exploration reveals endothelial inflammation as a common mechanism for stroke and coronary artery disease treatment of Danhong injection. Sci. Rep., 2017, 7(1), 15427.
[http://dx.doi.org/10.1038/s41598-017-14692-3] [PMID: 29133791]
[38]
Liu, L.; Wang, H. The recent applications and developments of bioinformatics and omics technologies in traditional Chinese medicine. Curr. Bioinform., 2019, 14(3), 200-210.
[http://dx.doi.org/10.2174/1574893614666190102125403]
[39]
Greenwell, M.; Rahman, P.K. Medicinal plants: Their use in anticancer treatment. Int. J. Pharm. Sci. Res., 2015, 6(10), 4103-4112.
[PMID: 26594645]
[40]
Zhang, D.; Zheng, J.; Ni, M.; Wu, J.; Wang, K.; Duan, X.; Zhang, X.; Zhang, B. Comparative efficacy and safety of Chinese herbal injections combined with the FOLFOX regimen for treating gastric cancer in China: A network meta-analysis. Oncotarget, 2017, 8(40), 68873-68889.
[http://dx.doi.org/10.18632/oncotarget.20320] [PMID: 28978164]
[41]
Lemonnier, T.; Dupré, A.; Jessus, C. The G2-to-M transition from a phosphatase perspective: A new vision of the meiotic division. Cell Div., 2020, 15(1), 9.
[http://dx.doi.org/10.1186/s13008-020-00065-2] [PMID: 32508972]
[42]
Yuan, K.; Wang, X.; Dong, H.; Min, W.; Hao, H.; Yang, P. Selective inhibition of CDK4/6: A safe and effective strategy for developing anticancer drugs. Acta Pharm. Sin. B, 2021, 11(1), 30-54.
[http://dx.doi.org/10.1016/j.apsb.2020.05.001] [PMID: 33532179]
[43]
Kalous, J.; Jansová, D.; Šušor, A. Role of cyclin-dependent kinase 1 in translational regulation in the M-phase. Cells, 2020, 9(7), 1568.
[http://dx.doi.org/10.3390/cells9071568] [PMID: 32605021]
[44]
Guo, C.; Kong, F.; Lv, Y.; Gao, N.; Xiu, X.; Sun, X. CDC20 inhibitor Apcin inhibits embryo implantation in vivo and in vitro. Cell Biochem. Funct., 2020, 38(6), 810-816.
[http://dx.doi.org/10.1002/cbf.3550] [PMID: 32458533]
[45]
Cheng, L.; Huang, Y.Z.; Chen, W.X.; Shi, L.; Li, Z.; Zhang, X.; Dai, X.Y.; Wei, J.F.; Ding, Q. Cell division cycle proteinising prognostic biomarker of breast cancer. Biosci. Rep., 2020, 40(5), BSR20191227.
[http://dx.doi.org/10.1042/BSR20191227] [PMID: 32285914]
[46]
Qiu, E.; Gao, Y.; Zhang, B.; Xia, T.; Zhang, Z.; Shang, G. Upregulation of cell division cycle 20 in cisplatin resistance-induced epithelial-mesenchymal transition in osteosarcoma cells. Am. J. Transl. Res., 2020, 12(4), 1309-1318.
[PMID: 32355543]
[47]
Hattori, Y.; Kikuchi, T.; Ozaki, K.I.; Onishi, H. Evaluation of in vitro and in vivo therapeutic antitumor efficacy of transduction of polo-like kinase 1 and heat shock transcription factor 1 small interfering RNA. Exp. Ther. Med., 2017, 14(5), 4300-4306.
[http://dx.doi.org/10.3892/etm.2017.5060] [PMID: 29067111]
[48]
Yang, X.; Chen, G.; Li, W.; Peng, C.; Zhu, Y.; Yang, X.; Li, T.; Cao, C.; Pei, H. Cervical cancer growth is regulated by a c-ABL–PLK1 signaling axis. Cancer Res., 2017, 77(5), 1142-1154.
[http://dx.doi.org/10.1158/0008-5472.CAN-16-1378] [PMID: 27899378]

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