Human Papillomavirus E6/E7-Specific siRNA Potentiates the Effect of Radiotherapy for Cervical Cancer in Vitro and in Vivo.
Human Papillomavirus E6/E7-Specific siRNA Potentiates the Effect of Radiotherapy for Cervical Cancer in Vitro and in Vivo.
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DOI：
10.3390/ijms160612243
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发表时间：
2015-05-29
影响因子：
5.6
通讯作者：
Shin YK
中科院分区：
文献类型：
--
作者：
Jung HS;Rajasekaran N;Song SY;Kim YD;Hong S;Choi HJ;Kim YS;Choi JS;Choi YL;Shin YK
HPV来源的E6和E7癌蛋白对TP53和Rb抑癌蛋白的功能失活可能是宫颈癌发生过程中的一个重要步骤。我们之前已经展示了siRNA技术选择性地沉默E6/E7癌基因，并证明合成的siRNAs可以特异性地阻断其在HPV阳性的宫颈癌细胞中的表达。在此，我们研究了E6/E7 siRNA候选分子作为放射增敏剂治疗宫颈癌的可能性。将HPVE6/E7siRNA导入HeLa和SiHa细胞，通过细胞存活率测定、流式细胞仪分析和衰老相关β半乳糖苷酶(SA-β-Gal)检测来评价E6/E7siRNA和放射联合作用的细胞毒效应。此外，我们还观察了照射联合静脉注射E6/E7 siRNA在体内异种移植模型中的作用。SiRNA和放射联合治疗有效地延缓了已建立的人宫颈癌细胞异种移植小鼠肿瘤的生长。此外，化学修饰的HPV16和18E6/E7 siRNA与放射联合使用对宫颈癌细胞的生长有强烈的抑制作用。我们的结果表明，在放疗的同时抑制HPVE6/E7癌基因的表达，可以增强人宫颈癌的抗肿瘤活性和放射增敏活性。
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.
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影响因子：
46.9
作者：
Haasnoot J;Westerhout EM;Berkhout B
通讯作者：
Berkhout B
影响因子：
14.9
作者：
Hainaut, P;Hernandez, T;Montesano, R
通讯作者：
Montesano, R
影响因子：
11.2
作者：
Maufort JP;Shai A;Pitot HC;Lambert PF
通讯作者：
Lambert PF
DOI：
10.1097/coc.0b013e31803377c8
发表时间：
2007-08-01
影响因子：
2.6
作者：
Garcia, Agustin A.;Blessing, John A.;Roman, Lynda D.
通讯作者：
Roman, Lynda D.
影响因子：
8
作者：
Butz, K;Ristriani, T;Hoppe-Seyler, F
通讯作者：
Hoppe-Seyler, F