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Effect of resveratrol combined with radiotherapy on cervical cancer Hela cell growth and migration by regulating PI3K/Akt/mTOR signaling pathway
Zhang Jianfu1, Zhang Yunjun2, Jiang Bengui3, Mei Haibing4, Zhong Huizhen5
1Department of Pharmacy, Ningbo Women's and Children's Hospital, Ningbo 315012, China; 2Department of Imaging, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China; 3Department of Gynecology, Ningbo Women's and Children's Hospital, Ningbo 315012, China; 4Department of Imaging, Ningbo Women's and Children's Hospital, Ningbo 315012, China; 5School of Medicine, Ningbo University, Ningbo 315211, China
AbstractObjective To evaluate the effect of resveratrol combined with γ-ray irradiation on the biological behavior of cervical cancer cells, and to explore its possible mechanism. Methods The proliferation of cell populations after different concentrations of resveratrol solution±γ-ray irradiation was detected by CCK-8 assay. Scratch test and Transwell chamber test were used to detect cell migration and invasion. Flow cytometry and Annexin V-FITC/PI double staining were employed to assess cell apoptosis. Western blot was performed to measure the expression levels of PI3K, Akt, p-Akt, mTOR and p-mTOR proteins. Results Compared with the normal control (NC) group, the resveratrol group±γ-ray irradiation could inhibit the proliferation, migration, and invasion and promote cell apoptosis of human cervical cancer Hela cells, and the combined effect was more obvious. Compared with the NC group, resveratrol and γ-ray irradiation could significantly down-regulate the expression levels of Bcl-2, PI3K, p-Akt and p-mTOR proteins, up-regulate the expression level of Bax protein, but did not significantly alter the expression levels of Akt and mTOR proteins in human cervic1255al cancer Hela cells. Conclusions Resveratrol combined with γ-ray irradiation can dramatically inhibit the proliferation, migration, invasion, and promote the apoptosis of cervical cancer Hela cells. The mechanism may be related to the inhibition of the PI3K/Akt/mTOR signaling pathway and down-regulating the expression levels of downstream related proteins.
Zhang Jianfu,Zhang Yunjun,Jiang Bengui et al. Effect of resveratrol combined with radiotherapy on cervical cancer Hela cell growth and migration by regulating PI3K/Akt/mTOR signaling pathway[J]. Chinese Journal of Radiation Oncology, 2021, 30(9): 956-960.
Zhang Jianfu,Zhang Yunjun,Jiang Bengui et al. Effect of resveratrol combined with radiotherapy on cervical cancer Hela cell growth and migration by regulating PI3K/Akt/mTOR signaling pathway[J]. Chinese Journal of Radiation Oncology, 2021, 30(9): 956-960.
[1] Wang F, Shan S, Huo Y, et al.MiR-155-5p inhibits PDK1 and promotes autophagy via the mTOR pathway in cervical cancer[J]. Int J Biochem Cell Biol, 2018, 99(1):91-99.DOI:10.1016/j.biocel.2018.04.005. [2] 黄君文,宋佳成,李燕,等.DCE-MRI联合ADC值对宫颈癌同步放、化疗患者疗效评估的临床应用研究[J]. 临床放射学杂志,2018, 37(6):985-988.DOI:10.13437/j.cnki.jcr.2018.06.025. Huang JW, Song JC, Li Y, et al.Clinical application of DCE-MRI combined with ADC value in evaluating the efficacy of simultaneous radiotherapy and chemotherapy in patients with cervical cancer[J]. J Clin Radiol, 2018, 37(6):985-988.DOI:10.13437/j.cnki.jcr.2018.06.025. [3] 王芳芳,廖思辉,陈运强,等.不同化疗药物联合同期放疗治疗局部中晚期宫颈癌的临床疗效及不良反应观察[J]. 广西医科大学学报,2019, 36(3):412-415.DOI:10.16190/j.cnki.45-1211/r.2019.03.021. Wang FF, Liao SH, Chen YQ, et al.Clinical efficacy and adverse reactions of different chemotherapy drugs combined with concurrent radiotherapy in the treatment of local advanced cervical cancer[J]. J Guangxi Med Univ, 2019, 36(3):412-415.DOI:10.16190/j.cnki.45-1211/r.2019.03.021. [4] 贾伟炜,赵映瑜,陈振武.酶解辅助法提取虎杖中白藜芦醇的研究[J]. 应用化工,2018, 47(6):1132-1136.DOI:10.16581/j.cnki.issn1671-3206.20180330.011. Jia WW, Zhao YY, Chen ZW.Study on extraction of resveratrol from Polygonum cuspidatum by enzymatic hydrolysis assisted method[J]. Appl Chem Indust, 2018, 47(6):1132-1136.DOI:10.16581/j.cnki.issn1671-3206.20180330.011. [5] 杨艳华, 周翔禹.白藜芦醇通过SDF-1/CXCR4信号通路诱导大肠癌细胞株SW480凋亡[J]. 临床消化病杂志, 2019, 31(4):227-231.DOI:10.3870/lcxh.j.issn.1005-541X.2019.04.08. Yang YH, Zhou XY.Aapoptosis induced by resveratrol via SDF-1/CXCR4 signaling pathway in colorectal cancer cell line SW480[J]. J Clin Gastroenterol, 2019, 31(4):227-231.DOI:10.3870/lcxh.j.issn.1005-541X.2019.04.08. [6] Zhang P, Li H, Yang B, et al.Biological significance and therapeutic implication of resveratrol-inhibited Wnt, Notch and STAT3 signaling in cervical cancer cells[J]. Genes Cancer, 2014, 5(6):154-164.DOI:10.18632/genesandcancer.15. [7] da Costa Araldi, Bordin FPR, Cadoná FC, et al.The in vitro radiosensitizer potential of resveratrol on MCF-7 breast cancer cells[J]. Chem Biol Interact, 2018, 282(1):85-92.DOI:10.1016/ j.cbi.2018.01.013. [8] Mirzapur P, Khazaei MR, Moradi MT, et al.Apoptosis induction in human breast cancer cell lines by synergic effect of raloxifene and resveratrol through increasing proapoptotic genes[J]. Life Sci, 2018, 205(1):45-53.DOI:10.1016/ j.lfs.2018.04.035. [9] Nivelle L, Aires V, Rioult D, et al.Molecular analysis of differential antiproliferative activity of resveratrol, epsilon viniferin and labruscol on melanoma cells and normal dermal cells[J]. Food Chem Toxicol, 2018, 116(Pt 8):323-334.DOI:10.1016/ j.fct.2018.04.043. [10] Dai H, Deng HB, Wang YH, et al.Resveratrol inhibits the growth of gastric cancer via the Wnt/β-catenin pathway[J]. Oncol Lett, 2018, 16(2):1579-1583.DOI:10.3892/ ol.2018.8772. [11] Rogers S, McCloy RA, Parker BL, et al.MASTL overexpression promotes chromosome instability and metastasis in breast cancer[J]. Oncogene, 2018, 37(33):4518-4533.DOI:10.1038/ s41388-018-0295-z. [12] Díaz-Serrano A, Angulo B, Dominguez C, et al.Genomic profiling of HER2-positive gastric cancer:PI3K/Akt/mTOR pathway as predictor of outcomes in HER2-positive advanced gastric cancer treated with trastuzumab[J]. Oncologist, 2018, 23(9):1092-1102.DOI:10.1634/ theoncologist.2017-0379. [13] Golob-Schwarzl N, Krassnig S, Toeglhofer AM, et al.New liver cancer biomarkers:PI3K/AKT/mTOR pathway members and eukaryotic translation initiation factors[J]. Eur J Cancer, 2017, 83(1):56-70.DOI:10.1016/ j.ejca.2017.06.003. [14] Zhu Y, Yu Z, Yu Z, et al.Acetylshikonin inhibits colorectal cancer growth via PI3K/Akt/mTOR signaling pathway[J]. Chin Med, 2018, 9(3):126-143.DOI:10.4236/cm.2018.93008. [15] 刘宁,刘世学.膀胱癌PI3K/Akt/mTOR信号通路与免疫抑制性细胞的相关分子机制研究[J]. 热带医学杂志,2019, 19(9):1086-1089.DOI:10.3969/j.issn.1672-3619.2019.09.006. Liu N, Liu SX.Study on the molecular mechanism of PI3K/Akt/mTOR signaling pathway and immunosuppressive cells in bladder cancer[J]. J Trop Med, 2019, 19(9):1086-1089.DOI:10.3969/j.issn.1672-3619.2019.09.006. [16] Huang W, Ding X, Ye H, et al.Hypoxia enhances the migration and invasion of human glioblastoma U87 cells through PI3K/Akt/mTOR/HIF-1α pathway[J]. Neuroreport, 2018, 29(18):1578-1585.DOI:10.1097/WNR.0000000000001156. [17] 何国慧.白藜芦醇通过调控PI3K/Akt/mTOR信号通路对人黑色素瘤A375细胞系增殖的影响研究[D]. 泸州:西南医科大学,2018. He GH.Study on the effect of resveratrol on the proliferation of human melanoma A375 cell line by regulating PI3K/Akt/mTOR signaling pathway[D]. Luzhou:Southwest Medical University, 2018. [18] 赵宇,祝瑜,吴浪,等.白藜芦醇对人肝癌HepG2细胞增殖及自噬作用的影响[J]. 中国生物制品学杂志,2018, 31(6):607-612.DOI:10.13200/j.cnki.cjb.002198. Zhao Y, Zhu Y, Wu L, et al.Effects of resveratrol on proliferation and autophagy of human hepatocellular carcinoma HepG2 cells[J]. Chin J Biol, 2018,31(6):607-612.DOI:10.13200/j.cnki.cjb.002198. [19] Wang XJ, Li YH.Inhibition of human chronic myelogenous leukemia K562 cell growth following combination treatment with resveratrol and imatinib mesylate[J]. Genetics Mol Res, 2015, 14(2):6413-6418.DOI:10.4238/2015.June.11.17. [20] 李雪玲,张凯敏,李娈英,等.白藜芦醇联合SB203580对宫颈癌细胞凋亡迁移的影响及机制[J]. 安徽医药,2019, 23(2):240-245.DOI:10.3969/j.issn.1009-6469.2019.02.007. Li XL, Zhang KM, Li YY, et al.Effect of resveratrol combined with SB203580 on apoptosis and migration of cervical cancer cells and its mechanism[J]. Anhui Med Pharm J, 2019, 23(2):240-245.DOI:10.3969/j.issn.1009-6469.2019.02.007.