龙胆苦苷对人上皮性卵巢癌细胞增殖、凋亡、迁移的影响及机制
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摘要
目的观察龙胆苦苷(GPS)对人上皮性卵巢癌HO8910细胞增殖、凋亡及迁移能力的影响,并探讨其可能的作用机制。方法培养人上皮性卵巢癌HO8910细胞,随机分为对照组、GPS低剂量组、GPS中剂量组、GPS高剂量组。对照组单纯加入0. 01%DMSO培养48 h,GPS低、中、高剂量组分别在加入10、20与40μmol/L GPS的DMEM培养液中培养48 h。采用MTT法观察各组细胞增殖能力,计算细胞增殖抑制率;采用TUNEL实验观察各组细胞凋亡情况,计算细胞凋亡率;采用细胞划痕实验观察各组细胞迁移能力,计算细胞迁移率。采用Western blotting法检测p-P38有丝分裂原激活的蛋白激酶(MAPK)、促凋亡蛋白B细胞白血病淋巴瘤相关蛋白(Bax)、抗凋亡蛋白B淋巴细胞/白血病-2(Bcl-2)的表达。结果与对照组相比,GPS中剂量组、GPS高剂量组细胞增殖抑制率、迁移率均降低,凋亡率均升高(P <0. 05或0. 01)。与对照组相比,GPS中剂量组、GPS高剂量组细胞内Bax、p-P38MAPK表达上调,Bcl-2表达下调(P <0. 05或0. 01)。结论 GPS具有抑制人上皮性卵巢癌HO8910细胞增殖及迁移并促进其凋亡的作用,其机制可能与激活P38 MAPK信号通路相关。
Objective To investigate the effects of gentiopicroside( GPS) on the proliferation,apoptosis,and migration of ovarian cancer cells. Methods The ovarian cancer cells HO8910 were cultured in vitro,and then were divided into the control group,low-dose,medium-dose,and high-dose GPS groups. The cells in the drug groups were treated with 10,20,and 40 μmol/L of GPS for 48 h,and the cells in the control group were only cultured in vitro with 0. 01% DMSO for48 h. MTT was used to detected the effect of GPS on proliferation of HO8910 cells; the apoptosis rate of HO8910 was detected by TUNEL; the cell scratch test was used to detected the effect of GPS on cell migration; and the phosphorylation level of P38 mitogen-activated protein kinase( p-P38 MAPK) and the expression of mitochondrial apoptosis pathway proteins( Bax),B-lymphocyte/leukemia-2( Bcl-2) protein were were detected by Western blotting. Results Compared with the control group,the proliferation inhibitory and migration rates of cells decreased significantly and the apoptosis rates increased in the medium-dose and high-dose GPS groups( P < 0. 05 or P < 0. 01). Compared with the control group,the expression of Bax3 and p-P38 MAPK was up-regulated,and the expression of Bcl-2 protein was down-regulated in the medium-dose and high-dose GPS groups( P < 0. 05 or P < 0. 01). Conclusion The GPS can inhibit the proliferation and migration of ovarian cancer cell lines and promote its apoptosis by activating the P38 MAPK pathway.
Objective To investigate the effects of gentiopicroside( GPS) on the proliferation,apoptosis,and migration of ovarian cancer cells. Methods The ovarian cancer cells HO8910 were cultured in vitro,and then were divided into the control group,low-dose,medium-dose,and high-dose GPS groups. The cells in the drug groups were treated with 10,20,and 40 μmol/L of GPS for 48 h,and the cells in the control group were only cultured in vitro with 0. 01% DMSO for48 h. MTT was used to detected the effect of GPS on proliferation of HO8910 cells; the apoptosis rate of HO8910 was detected by TUNEL; the cell scratch test was used to detected the effect of GPS on cell migration; and the phosphorylation level of P38 mitogen-activated protein kinase( p-P38 MAPK) and the expression of mitochondrial apoptosis pathway proteins( Bax),B-lymphocyte/leukemia-2( Bcl-2) protein were were detected by Western blotting. Results Compared with the control group,the proliferation inhibitory and migration rates of cells decreased significantly and the apoptosis rates increased in the medium-dose and high-dose GPS groups( P < 0. 05 or P < 0. 01). Compared with the control group,the expression of Bax3 and p-P38 MAPK was up-regulated,and the expression of Bcl-2 protein was down-regulated in the medium-dose and high-dose GPS groups( P < 0. 05 or P < 0. 01). Conclusion The GPS can inhibit the proliferation and migration of ovarian cancer cell lines and promote its apoptosis by activating the P38 MAPK pathway.
引文
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[10]郭海凤,张善玉,朴惠顺.关龙胆乙醇提取物对小鼠S_(180)肉瘤的抑制增殖作用[J].延边大学医学学报,2009,32(4):256-257.
[11]赵忠伟,韩鹏.龙胆苦苷对人肝癌HepG2细胞的抑制作用[J].中国老年学杂志,2016,36(24):6082-6083.
[12]Du W,Wu PF,Qing LM,et al.Systemic and flap inflammatory response associates with thrombosis in flap venous crisis[J].Inflammation,2015,38(1):298-304.
[13]龙玲,周琦,张笠.p38MAPK信号传导通路与卵巢癌关系研究进展[J].国际妇产科学杂志,2017,44(5):494-498.
[14]Alibek K,Irving S,Sautbayeva Z,et al.Disruption of Bcl-2 and Bcl-xL by viral proteins as a possible cause of cancer[J].Infect A-gent Cancer,2014,9:44.
[15]许雅鑫,吴彬,游锦梅,等.ATM/ATR-p53-Bcl2/Bax通路在PRPS2表达下调致HCT116凋亡中的作用研究[J].中国药物与临床,2015,15(7):933-934.
[2]Niu YT,Zhao YP,Jiao YF,et al.Protective effect of gentiopicroside against dextran sodium sulfate induced colitis in mice[J].Int Immunopharmacol,2016,39:16-22.
[3]Tang X,Yang Q,Yang F,et al.Target profiling analyses of bile acids in the evaluation of hepatoprotective effect of gentiopicroside on ANIT-induced cholestatic liver injury in mice[J].J Ethnopharmacol,2016,194:63-71.
[4]Huang XJ,Li J,Mei ZY,et al.Gentiopicroside and sweroside from veratrilla baillonii Franch.induce phosphorylation of Akt and suppress Pck1 expression in hepatoma cells[J].Biochem Cell Biol,2016,94(3):270-278.
[5]Yang Y,Duan W,Liang Z,et al.Curcumin attenuates endothelial cell oxidative stress injury through Notch signaling inhibition[J].Cell Signal,2013,25(3):615-629.
[6]Ming L,Jin F,Huang P,et al.Licochalcone A up-regulates of Fas L in mesenchymal stem cells to strengthen bone formation and increase bone mass[J].Sci Rep,2014,4:7209.
[7]Kumar R.Steroid hormone receptors and prostate cancer:role of structural dynamics in therapeutic targeting[J].Asian J Androl,2016,18(5):682-686.
[8]仇小敏,王佳贺.甘草查尔酮A对卵巢癌细胞株HO8910增殖、凋亡的影响及其机制[J].山东医药,2018,58(19):1-4.
[9]乔慧莲,陈浩,陈文豪,等.龙胆苦甙后处理对心脏缺血再灌注损伤的防治作用[J].山东医药,2013,53(35):1-4.
[10]郭海凤,张善玉,朴惠顺.关龙胆乙醇提取物对小鼠S_(180)肉瘤的抑制增殖作用[J].延边大学医学学报,2009,32(4):256-257.
[11]赵忠伟,韩鹏.龙胆苦苷对人肝癌HepG2细胞的抑制作用[J].中国老年学杂志,2016,36(24):6082-6083.
[12]Du W,Wu PF,Qing LM,et al.Systemic and flap inflammatory response associates with thrombosis in flap venous crisis[J].Inflammation,2015,38(1):298-304.
[13]龙玲,周琦,张笠.p38MAPK信号传导通路与卵巢癌关系研究进展[J].国际妇产科学杂志,2017,44(5):494-498.
[14]Alibek K,Irving S,Sautbayeva Z,et al.Disruption of Bcl-2 and Bcl-xL by viral proteins as a possible cause of cancer[J].Infect A-gent Cancer,2014,9:44.
[15]许雅鑫,吴彬,游锦梅,等.ATM/ATR-p53-Bcl2/Bax通路在PRPS2表达下调致HCT116凋亡中的作用研究[J].中国药物与临床,2015,15(7):933-934.
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