目的 研究DNA去甲基化藥物地西他濱與Zeste基因增強(qiáng)子同源物2（enhancer of Zeste Homolog 2，EZH2）抑制劑GSK126聯(lián)合應(yīng)用對(duì)膀胱癌誘導(dǎo)"病毒模擬"免疫應(yīng)答的抗腫瘤作用。方法 將膀胱癌細(xì)胞株T24分為4組，對(duì)照組、地西他濱單藥組、GSK126單藥組、地西他濱與GSK126聯(lián)合用藥組。用細(xì)胞倍增時(shí)間測(cè)定T24細(xì)胞的增殖能力，用藥物聯(lián)合分析計(jì)算聯(lián)合指數(shù)（CI），用實(shí)時(shí)熒光定量PCR（qRT-PCR）檢測(cè)ERV-Fc1、ERV-W、IFIT2、IRF7、MDA5、RGH2和RIG1內(nèi)源性逆轉(zhuǎn)錄病毒基因（endogenous retrovirus，ERV）的表達(dá)。結(jié)果 地西他濱藥物聯(lián)合應(yīng)用對(duì)T24細(xì)胞有顯著的抑制作用（P<0.05），兩者之間具有協(xié)同作用（CI<1），7個(gè)ERVs的表達(dá)上調(diào)。結(jié)論 地西他濱聯(lián)合GSK126對(duì)膀胱癌T24細(xì)胞有協(xié)同增殖抑制作用，其機(jī)制可能與誘導(dǎo)"病毒模擬"有關(guān)。

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".

R965

中國(guó)博士后基金資助項(xiàng)目（2016M591399）；天津市教委自然科學(xué)基金重點(diǎn)項(xiàng)目（2019ZD031）；泉州市科技計(jì)劃項(xiàng)目（2018N111S、2019N076S）