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白藜芦醇诱导人前列腺癌DU145细胞凋亡的作用机制

李伟, 许学芬

李伟, 许学芬. 白藜芦醇诱导人前列腺癌DU145细胞凋亡的作用机制[J]. 中国药科大学学报, 2018, 49(6): 711-717. DOI: 10.11665/j.issn.1000-5048.20180612
引用本文: 李伟, 许学芬. 白藜芦醇诱导人前列腺癌DU145细胞凋亡的作用机制[J]. 中国药科大学学报, 2018, 49(6): 711-717. DOI: 10.11665/j.issn.1000-5048.20180612
LI Wei, XU Xuefen. Mechanism of resveratrol induced apoptosis on human prostate cancer cell line DU145[J]. Journal of China Pharmaceutical University, 2018, 49(6): 711-717. DOI: 10.11665/j.issn.1000-5048.20180612
Citation: LI Wei, XU Xuefen. Mechanism of resveratrol induced apoptosis on human prostate cancer cell line DU145[J]. Journal of China Pharmaceutical University, 2018, 49(6): 711-717. DOI: 10.11665/j.issn.1000-5048.20180612

白藜芦醇诱导人前列腺癌DU145细胞凋亡的作用机制

基金项目: 国家自然科学基金资助项目(No.81703542);江苏高校优势学科(中西结合)资助项目

Mechanism of resveratrol induced apoptosis on human prostate cancer cell line DU145

  • 摘要: 研究白藜芦醇诱导人前列腺癌DU145细胞凋亡的作用机制。采用MTT检测细胞增殖情况,活性氧试剂盒分析细胞内ROS水平;流式细胞术观察细胞凋亡和细胞周期的变化。Western blot检测凋亡相关蛋白以及相关通路蛋白表达。结果表明,经不同药物浓度处理,白藜芦醇可以诱导DU145细胞发生凋亡,使细胞周期阻滞于G0/G1期,提高细胞内ROS水平,降低细胞内线粒体膜电位水平,并呈剂量依赖性。白藜芦醇通过上调Bax蛋白的表达和抑制Bcl-2蛋白表达,促使Bax/Bcl-2比值升高,激活Caspase级联反应从而诱导细胞发生凋亡。进一步研究发现白藜芦醇可以升高细胞内ROS水平,降低线粒体膜电位水平,从而通过线粒体途径诱导DU145细胞发生凋亡。因此,白藜芦醇可能通过ROS-线粒体途径诱导人前列腺癌DU145细胞凋亡。
    Abstract: In this study, apoptotic mechanism of resveratrol against human prostatic carcinoma DU145 cells was investigated. MTT was used to measure cell growth and proliferation. Reactive oxygen species(ROS)kit was used to analyze ROS level. Cell apoptosis and cell cycle analysis were observed by flow cytometry. Protein expression levels of apoptosis and pathway associated were analyzed by Western blot. The result shows that DU145 cells treated with different resveratrol concentrations suffered apoptosis, cycle arrest in G0/G1 phase, ROS increase in the cell and a decrease in mitochondrial membrane potential(MMP, ΔΨm), in a concentration-dependent manner. Resveratrol inhibited the expression of Bcl-2 protein via up-regulating Bax protein, thus increasing the ratio of Bax/Bcl-2, activating Caspase reaction and led apoptosis ultimately. Further investigation confirmed that resveratrol increased ROS level, decreased MMP and consequently induced apoptosis via michondrial-mediated pathway in DU145 cells. Therefore resveratrol may induce apoptosis via ROS-michondrial pathway in DU145 cells.
  • [1] Stang A,Jöckel KH.The impact of cancer screening on all-cause mortality[J].Dtsch Arztebl Int,2018,115(29/30):481-486.
    [2] DeSantis CE, Siegel RL, Sauer AG, et al. Cancer statistics for African Americans,2016:progress and opportunities in reducing racial disparities[J].CA Cancer J Clin,2016,66(4):290-308.
    [3] Akaza H,Onozawa M,Hinotsu S.Prostate cancer trends in Asia[J].World J Urol,2017,1(6):1-7.
    [4] Kang S,Zhao Y,Wang L,et al.Lack of association between the risk of prostate cancer and vitamin D receptor Bsm I polymorphism:a meta-analysis of 27 published studies[J].Cancer Manag Res,2018,10:2377-2387.
    [5] Tang S,Han H,Dong F,et al.Prostate cancer incidentally discovered at the time of radical cystoprostatectomy does not decrease overall survival:results from a large Chinese medical center[J].Int Braz J Urol,2018,44(2):258-266.
    [6] Aggarwal BB,Bhardwaj A,Aggarwal RS,et al.Role of resveratrol in prevention and therapy of cancer:preclinical and clinical studies[J].Anti Cancer Res,2004,24(5A):2783-2840.
    [7] Wu X,Wu X,Xu Y,et al.Resveratrol induces apoptosis in SGC-7901 gastric cancer cells[J].Oncol Lett,2018,16(3):2949-2956.
    [8] Rasheduzzaman M,Jeong JK,Park SY.Resveratrol sensitizes lung cancer cell to TRAIL by p53 independent and suppression of Akt/NF-κB signaling[J].Life Sci,2018,48(2):208-220.
    [9] Zhou X, Zhao Y, Wang J, et al. Resveratrol represses estrogen-induced mammary carcinogenesis through NRF2-UGT1A8-estrogen metabolic axis activation[J].Biochem Pharmacol,2018,155:252-263.
    [10] Yang C,Gundala SR,Rao M,et al.Synergistic interactions among flavonoids and acetogenins in Graviola(Annona muricata)leaves confer protection against prostate cancer[J].Carcinogenesis,2015,36(6):656-665.
    [11] Lall RK,Syed DN,Adhami VM,et al.Dietary polyphenols in prevention and treatment of prostate cancer[J].Int J Mol Sci,2015,16(2):3350-3376.
    [12] Bishayee A.Cancer prevention and treatment with resveratrol:from rodent studies to clinical trials[J].Cancer Prev Res,2009,2(5):409-418.
    [13] Anwar DM, Khattab SN, Helmy MW, et al. Lactobionic/folate dual-targeted amphiphilic maltodextrin-based micelles for targeted codelivery of sulfasalazine and resveratrol to hepatocellular carcinoma[J].Bioconjug Chem,2018,29(9):3026-3041.
    [14] Huang C,Freter C.Lipid metabolism,apoptosis and cancer therapy[J].Int J Mol Sci,2015,16(1):924-949.
    [15] Han MY, Nie JW, Li YY, et al. Downregulation of NGAL is required for the inhibition of proliferation and the promotion of apoptosis of human gastric cancer MGC-803 cells[J].Cell Physiol Biochem,2018,50(2):694-705.
    [16] Mou Z,Xu X,Dong M,et al.MicroRNA-148b acts as a tumor suppressor in cervical cancer by inducing G1/S-phase cell cycle arrest and apoptosis in a caspase-3-dependent manner[J].Med Sci Monit,2016,22:2809-2815.
    [17] Birame B M,Jigui W,Fuxian Y,et al.Potentiation of apoptin-induced apoptosis by cecropin B-like antibacterial peptide ABPs1 in human HeLa cervical cancer cell lines is associated with membrane pore formation and caspase-3 activation[J].J Microbiol Biotechnol,2014,24(6):756-764.
    [18] Khalil H,Rosenblatt N,Liaudet L,et al.The role of endogenous and exogenous RasGAP-derived fragment N in protecting cardiomyocytes from peroxynitrite-induced apoptosis[J].Free Radic Biol Med,2012,53(4):926-935.
    [19] Heng S,Reineck P,Vidanapathirana A,et al.Rationally designed probe for reversible sensing of zinc and application in cells[J].ACS Omega,2017,2(9):6201-6210.
    [20] Shi Q,Song QQ,Sun P,et al.Infection of prions and treatment of PrP106-126 alter the endogenous status of protein 14-3-3 and trigger the mitochondrial apoptosis possibly via activating Bax pathway[J].Mol Neurobiol,2014,49(2):840-851.
    [21] Deng S,Tang S,Zhang S,et al.Furazolidone induces apoptosis through activating reactive oxygen species-dependent mitochondrial signaling pathway and suppressing PI3K/Akt signaling pathway in HepG2 cells[J].Food Chem Toxicol,2015,75:173-186.
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  • 刊出日期:  2018-12-24

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