NDLI: 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

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

Content Provider	MDPI
Author	Jung, Hun Rajasekaran, Nirmal Song, Sang Kim, Young Hong, Sungyoul Choi, Hyuck Choi, Jong-Sun Choi, Yoon-La Shin, Young
Abstract	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.
File Size	2795520
Ending Page	12260
Page Count	18
Starting Page	12243
File Format	PDF
e-ISSN	14220067
DOI	10.3390/ijms160612243
Journal	International Journal of Molecular Sciences
Issue Number	6
Volume Number	16
Language	English
Publisher Date	2015-05-29
Access Restriction	Open
Subject Keyword	E6 E7 siRNA Concurrent Chemoradiation therapy (CCRT) radiotherapy radiosensitizer cervical cancer
Content Type	Text
Resource Type	Article

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