Effect of celastrol combined medication on the inhibition of HepG2 cell proliferation

ZHANG Xue; OUYANG Huizhi; XU Wei; WANG Xiaoying

doi:10.11665/j.issn.1000-5048.20200209

Journal of China Pharmaceutical University > 2020 > 51(2): 185-192. > DOI: 10.11665/j.issn.1000-5048.20200209

ZHANG Xue, OUYANG Huizhi, XU Wei, WANG Xiaoying. Effect of celastrol combined medication on the inhibition of HepG2 cell proliferation[J]. Journal of China Pharmaceutical University, 2020, 51(2): 185-192. DOI: 10.11665/j.issn.1000-5048.20200209

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Effect of celastrol combined medication on the inhibition of HepG2 cell proliferation

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To study the inhibitory effect of celastrol respectively combined with glycyrrhetic acid, paclitaxel, and rhein on the proliferation of human hepatoma cell line HepG2. The MTT method was used to detect the survival rate of HepG2 cells. The cooperativity index(CI)and Jin′s formula method were used to determine the synergistic effect. Apoptosis and cell cycle arrest were detected, too. The results show that celastrol, glycyrrhetinic acid, rhein, and paclitaxel alone can inhibit the proliferation of HepG2 cells, respectively. Combination with glycyrrhetic acid, paclitaxel, and rhein, respectively, the inhibitory effect of celastrol on the proliferation of HepG2 cells was significantly enhanced. And the synergistic effect on the proliferation inhibition of HepG2 cells in some concentrations was displayed in the experiment. The cell apoptosis rate was improved(P< 0. 01)and more cells were arrested in G₂/M phase. Celastrol respectively combined with glycyrrhetic acid, paclitaxel, and rhein displayed a synergistic inhibitory effect on the proliferation of HepG2 cells, and the effect was related to inducing cell apoptosis and increasing the cell cycle arrest in G₂/M phase.
- celastrol,
- rhein,
- paclitaxel,
- glycyrrhetic acid,
- HepG2 cells,
- combined medication,
- synergy effect

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[1]	Kannaiyan R, Shanmugam MK, Sethi G. Molecular targets of celastrol derived from Thunder of God Vine:potential role in the treatment of inflammatory disorders and cancer[J].Cancer Lett,2011,303(1):9-20.
[2]	Sha M,Ye J,Zhang LX,et al.Celastrol induces apoptosis of gastric cancer cells by miR-146a inhibition of NF-kappaB activity[J].Cancer Cell Int,2013,13(1):50.
[3]	Zhao X,Gao S,Ren H,et al.Inhibition of autophagy strengthens celastrol-induced apoptosis in human pancreatic cancer in vitro and in vivo models[J].Curr Mol Med,2014,14(4):555-563.
[4]	Han X,Sun S,Zhao M,et al.Celastrol stimulates hypoxia-inducible factor-1 activity in tumor cells by initiating the ROS/Akt/p70S6K signaling pathway and enhancing hypoxia-inducible factor-1alpha protein synthesis[J].PLoS One,2014,9(11):e112470.
[5]	Huang L,Zhang Z,Zhang S,et al.Inhibitory action of celastrol on hypoxia-mediated angiogenesis and metastasis via the HIF-1alpha pathway[J].Int J Mol Med,2011,27(3):407-415.
[6]	Du Q,Bian XL,Xu XL,et al.Role of mitochondrial permeability transition in human hepatocellular carcinoma HepG-2 cell death induced by rhein[J].Fitoterapia,2013,91:68-73.
[7]	Nasongkla N,Nittayacharn P,Rotjanasitthikit A,et al.Paclitaxel-loaded polymeric depots as injectable drug delivery system for cancer chemotherapy of hepatocellular carcinoma[J].Pharm Dev Technol,2017,22(5):652-658.
[8]	Zhang YQ,Cai Y,Liu Y,et al.Glycyrrhetinic acid selectively inhibits proliferation of hepatocellular carcinoma cells in vitro[J].J South Med Univ(南方医科大学学报),2018,20,38(4):477-482.
[9]	Liu QY,Gao TS,Yu SJ.Preliminary study about effect of rhein treatment on rat non-alcoholic fatty liver disease[J].J Liaoning Univ TCM(辽宁中医药大学学报),2015,17(7):30-32.
[10]	Yang XY,Su XL.Pathways and their mechanisms of hepatoprotective effect of glycyrrhetinic acid[J].Chin J Histochem Cytochem(中国组织化学与细胞化学杂志),2019,(1):66-70.
[11]	Li MF,Guan H,Gan XF.Clinical trial of paclitaxel combined with sorafenib in the treatment of hepatocellular carcinoma[J].Chin J Clin Pharmacol(中国临床药理学杂志),2016,32(11):969-971.
[12]	Wang SQ,Zhu YZ,Zheng XB.Study and application of Chou-Talalay method for anti-tumor drug combination[J].Chin J Mod Appl Pharm(中国现代应用药学),2013,30(4):449-453.
[13]	Zhao J.An experimental study of the synergistic effect of TRAIL combined with cisplatin in NSCLC cell lines[D].Chengdu:Sichuan University,2007.
[14]	Yang H,Chen D,Cui QC,et al.Celastrol,a triterpene extracted from the Chinese “Thunder of God Vine”,is a potent proteasome inhibitor and suppresses human prostate cancer growth in nude mice[J].Cancer Res,2006,66(9):4758-4765.
[15]	Chen Z.The molecular mechanism of cardiac toxicity of tripterine(雷公藤红素致心脏毒性的分子机制研究)[D].Nanjing:Nanjing Normal University,2012.
[16]	Li ZX,Jin BY.Study on sodium glycodeoxycholate/DSPE-mPEG 2000 bionic mixed micelles loaded with celastrol for treating prostate cancer in vitro and in vivo[J].Chin Med Mat(中药材),2018,41(6):1423-1429.
[17]	Zhang L,Zhou JP,Yao J.Preparation and properties ofpaclitaxel-loaded glycyrhetinic acid-modified hyaluronic acid nanoparticles[J].J China Pharm Univ(中国药科大学学报),2012,43(3):226-230.
[18]	Du Q,Bian XL,Xu XL,et al.Role of mitochondrial permeability transition in human hepatocellular carcinoma HepG-2 cell death induced by rhein[J].Fitoterapia,2013,91:68-73.
[19]	Wang DD,Koramagazi A,Mao Y,et al.Rhein induces apoptosis in L-02 cells via reactive oxygen species-independent endoplasmic reticulum stress pathway[J].J China Pharm Univ(中国药科大学学报),2016,47(2):215-221.
[20]	Lu L,Guo QL,Zhai L.Advances of Src kinase family and paclitaxel resistance[J].J China Pharm Univ(中国药科大学学报),2017,48(4):377-383.
[21]	Xie GE,Du JC,Xu X.Inhibitory effect of celastrol on the growth of taxol-resistant breast cancer cells[J].J Guangdong Pharm Univ(广东药学院学报),2016,(3):335-338.

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