目的 研究DNA去甲基化藥物地西他濱與Zeste基因增強子同源物2（enhancer of Zeste Homolog 2，EZH2）抑制劑GSK126聯(lián)合應(yīng)用對膀胱癌誘導(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)胞倍增時間測定T24細(xì)胞的增殖能力，用藥物聯(lián)合分析計算聯(lián)合指數(shù)（CI），用實時熒光定量PCR（qRT-PCR）檢測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ERVs的表達(dá)上調(diào)。結(jié)論 地西他濱聯(lián)合GSK126對膀胱癌T24細(xì)胞有協(xié)同增殖抑制作用，其機制可能與誘導(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".

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中國博士后基金資助項目（2016M591399）；天津市教委自然科學(xué)基金重點項目（2019ZD031）；泉州市科技計劃項目（2018N111S、2019N076S）