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首页> 外文期刊>International Journal of Molecular Sciences >Human Papillomavirus E6/E7-Specific siRNA Potentiates the Effect of Radiotherapy for Cervical Cancer in Vitro and in Vivo
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Human Papillomavirus E6/E7-Specific siRNA Potentiates the Effect of Radiotherapy for Cervical Cancer in Vitro and in Vivo

机译：人乳头瘤病毒E6 / E7特异的siRNA增强了宫颈癌放射治疗的体内和体外效果。

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The functional inactivation of TP53 and Rb tumor suppressor proteins by the HPV-derived E6 and E7 oncoproteins is likely an important step in cervical carcinogenesis. We have previously shown siRNA technology to selectively silence both E6/E7 oncogenes and demonstrated that the synthetic siRNAs could specifically block its expression in HPV-positive cervical cancer cells. Herein, we investigated the potentiality of E6/E7 siRNA candidates as radiosensitizers of radiotherapy for the human cervical carcinomas. HeLa and SiHa cells were transfected with HPV E6/E7 siRNA; the combined cytotoxic effect of E6/E7 siRNA and radiation was assessed by using the cell viability assay, flow cytometric analysis and the senescence-associated β-galactosidase (SA-β-Gal) assay. In addition, we also investigated the effect of combined therapy with irradiation and E6/E7 siRNA intravenous injection in an in vivo xenograft model. Combination therapy with siRNA and irradiation efficiently retarded tumor growth in established tumors of human cervical cancer cell xenografted mice. In addition, the chemically-modified HPV16 and 18 E6/E7 pooled siRNA in combination with irradiation strongly inhibited the growth of cervical cancer cells. Our results indicated that simultaneous inhibition of HPV E6/E7 oncogene expression with radiotherapy can promote potent antitumor activity and radiosensitizing activity in human cervical carcinomas.
机译：HPV衍生的E6和E7癌蛋白对TP53和Rb肿瘤抑制蛋白的功能失活可能是宫颈癌发生过程中的重要一步。我们之前已经显示了siRNA技术可以选择性沉默两个E6 / E7癌基因，并证明合成的siRNA可以特异性阻断其在HPV阳性宫颈癌细胞中的表达。在这里，我们调查了E6 / E7 siRNA候选物作为人类宫颈癌放疗放射增敏剂的潜力。用HPV E6 / E7 siRNA转染HeLa和SiHa细胞; E6 / E7 siRNA和放射的联合细胞毒性作用通过细胞活力测定，流式细胞术分析和衰老相关的β-半乳糖苷酶（SA-β-Gal）测定进行评估。此外，我们还研究了在体内异种移植模型中联合放射治疗和E6 / E7 siRNA静脉注射联合治疗的效果。 siRNA和放射线的联合治疗有效抑制了人类宫颈癌细胞异种移植小鼠已建立肿瘤中的肿瘤生长。此外，化学修饰的HPV16和18 E6 / E7汇集的siRNA与辐射结合可强烈抑制宫颈癌细胞的生长。我们的结果表明，放疗同时抑制HPV E6 / E7癌基因表达可以促进人宫颈癌的有效抗肿瘤活性和放射增敏活性。

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