地西他滨联合GSK126通过诱导“病毒模拟”对人膀胱癌T24细胞的抑制作用研究

Inhibitory effect of decitabine combined with GSK126 on T24 cells by inducing “viral mimicry”

目的研究DNA去甲基化药物地西他滨与Zeste基因增强子同源物2(enhancer of Zeste Homolog 2,EZH2)抑制剂GSK126联合应用对膀胱癌诱导"病毒模拟"免疫应答的抗肿瘤作用。方法将膀胱癌细胞株T24分为4组,对照组、地西他滨单药组、GSK126单药组、地西他滨与GSK126联合用药组。用细胞倍增时间测定T24细胞的增殖能力,用药物联合分析计算联合指数(CI),用实时荧光定量PCR(qRT-PCR)检测ERV-Fc1、ERV-W、IFIT2、IRF7、MDA5、RGH2和RIG1内源性逆转录病毒基因(endogenous retrovirus,ERV)的表达。结果地西他滨药物联合应用对T24细胞有显著的抑制作用(P<0.05),两者之间具有协同作用(CI<1),7个ERVs的表达上调。结论地西他滨联合GSK126对膀胱癌T24细胞有协同增殖抑制作用,其机制可能与诱导"病毒模拟"有关。

Objective To study the anti-tumor effect of DNA demethylation inhibitor decitabine combined with EZH2 inhibitor GSK126 in "viral mimicry" immune response of bladder cancer. Methods The inhibitory effects of decitabine, GSK126, decitabine combined with GSK126 on human bladder cancer cell line T24 were determined by doubling time, the combination index(CI) was calculated by medicine combination analysis, and seven endogenous retroviruses(ERVs) of ERV-Fc1, ERV-W, IFIT2, IRF7, MDA5, RGH2 and RIG1 were detected by qRT-PCR. Results The combination of the two inhibitors had a significant inhibitory effect on T24 cells(P < 0.05), and there was a synergistic effect of the two inhibitors(CI < 1). The expression of seven ERVs was up-regulated. Conclusion Decitabine combined with GSK126 can synergisticly inhibit proliferation of bladder cancer, and the mechanism may be related to the induction of "viral mimicry".