Human Papillomavirus E6/E7-Specific siRNA Potentiates the Effect of Radiotherapy for Cervical Cancer in Vitro and in Vivo

International Journal of Molecular Sciences

Hun Soon Jung⁴  Nirmal Rajasekaran⁴  Sang Yong Song¹  Young Deug Kim⁶  Sungyoul Hong⁴  Hyuck Jae Choi³  Young Seok Kim⁵  Jong-Sun Choi²  Yoon-La Choi¹  Young Kee Shin⁴ 

[1] Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea; E-Mails:;The Center for Anti-cancer CDx, N-Bio, Seoul National University, Seoul 151-742, Korea; E-Mail:;Department of Radiology, Kangwon National University Hospital, Kangwon-do 200-722, Korea; E-Mail:;Research Institute of Pharmaceutical Science, Department of Pharmacy, College of Pharmacy, Seoul National University, Seoul 151-742, Korea; E-Mails:;Department of Radiation Oncology, Asan Medical Center, College of Medicine, University of Ulsan, Seoul 138-736, Korea; E-Mail:;ABION Inc. R&D Center, 9th Floor, HanWha Biz Metro Bldg, 242 Digital-ro, Guro-gu, Seoul 152-733, Korea; E-Mail:

关键词: E6;    E7;    siRNA;    Concurrent Chemoradiation therapy (CCRT);    radiotherapy;    radiosensitizer;    cervical cancer;   

DOI  :  10.3390/ijms160612243

来源: mdpi

【 摘 要 】

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.

【 授权许可】

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© 2015 by the authors; licensee MDPI, Basel, Switzerland.