黄腐酚类似物通过cAMP/Wnt/β-catenin信号通路抑制卵巢癌细胞增殖降低对顺铂的耐药性

Xanthohumol analogues inhibite ovarian cancer cell proliferation and reduce the resistance of cisplatin through cAMP/Wnt/β-catenin signaling pathway

目的:探究黄腐酚(xanthohumol,XN)类似物通过cAMP/Wnt/β-catenin信号通路调控卵巢癌细胞增殖的作用及对顺铂耐药性的影响。方法:以人卵巢癌细胞株HO-8910为研究材料,分为不同浓度(0、5、7.5、15、20μmol/L)黄腐酚类似物组、对照组、顺铂组、黄腐酚类似物+顺铂组。采用四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)法、实时荧光定量酶链式反应(quantitative real-time polymerase chain reaction,qRT-PCR)、蛋白免疫印迹法(Western blot,WB)检测黄腐酚类似物对HO-8910细胞增殖及对顺铂耐药性的影响。结果:与对照组比,黄腐酚类似物能够明显抑制HO-8910细胞增殖,差异具有统计学意义(P<0.05);黄腐酚类似物a13+顺铂组HO-8910细胞对顺铂的半数抑制浓度(half maximal inhibitory concentration,IC_(50))显著低于顺铂组,细胞活性抑制率(inhibition rate,IR)显著高于顺铂组,差异具有统计学意义(P<0.05);PKIβ(cAMP抑制剂)、IWP-2(Wnt/β-catenin抑制剂)可降低黄腐酚类似物a13对HO-8910细胞增殖的抑制作用,逆转黄腐酚类似物a13抑制HO-8910细胞对顺铂的耐药作用,差异具有统计学意义(P<0.05)。结论:黄腐酚类似物可提高顺铂对卵巢癌细胞增殖的抑制作用,降低细胞对顺铂的耐药性,作用机制与激活cAMP/Wnt/β-catenin信号通路有关。

Objective:To explore the effects of xanthohumol(XN)analogues on ovarian cancer cell proliferation and cisplatin resistance through cAMP/Wnt/β-catenin signaling pathway.Methods:Human ovarian cancer cell line HO-8910 was divided into XN analogue group,control group,cisplatin group and XN analogues+cisplatin group with different concentrations(0,5,7.5,15,20μmol/L).Methyl thiazolyl tetrazolium(MTT),quantitative real-time polymerase chain reaction(qRT-PCR)and Western blot(WB)were used to detect the effects of XN analogues on the proliferation and cisplatin resistance of HO-8910 cells.Results:Compared with the control group,XN analogues can obviously promote inhibit the proliferation of HO-8910 cells,and the difference is statistically significant(P<0.05).The half maximum inhibitory concentration(IC_(50))of HO-8910 cells in XN analogue a13+cisplatin group was significantly lower than that in cisplatin group,and the inhibition rate(IR)of cell activity was significantly higher than that in cisplatin group(P<0.05).PKIβ(cAMP inhibitor)and IWP-2(Wnt/β-catenin inhibitor)can reduce the inhibitory effect of XN analogues on proliferation of HO-8910 cells,and reverse the inhibitory effect of XN analogue a13 on cisplatin resistance of HO-8910 cells,with statistical significance(P<0.05).Conclusion:Xanthohumol analogues can enhance the inhibitory effect of cisplatin on ovarian cancer cell proliferation and reduce the drug resistance of ovarian cancer cells to cisplatin.The mechanism of action is related to the activation of cAMP/Wnt/β-catenin signaling pathway.