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The synergistic therapeutic effect of cisplatin with Human Papillomavirus E6/E7 short interfering RNA on cervical cancer cell lines in vitro and in vivo

Cited 27 time in Web of Science Cited 28 time in Scopus
Authors
Jung, Hun Soon; Erkin, Ozgur Cem; Kwon, Mi Jeong; Kim, Seok Hyung; Jung, Jae In; Oh, Yu-Kyoung; Her, Song Wook; Ju, Woong; Choi, Yoon-La; Song, Sang Yong; Kim, Joong Kyu; Kim, Young Deug; Shim, Ga Yong; Shin, Young Kee
Issue Date
2012-04
Publisher
UICC
Citation
International Journal of Cancer; Vol.130(8); pp. 1925-1936
Keywords
human papillomaviruscisplatin (CDDP) chemotherapyHPV E6/E7 siRNAchemosensitizercervical carcinoma
Abstract
Human papillomavirus (HPV) types 16 and 18 are the major etiologic factors in the development of cervical epithelial neoplasia. Our study was designed to validate antiviral short interfering RNA (siRNA) targeting the E6 and E7 oncogenes as a potential chemosensitizer of cisplatin (cis-diaminedichloroplatinum II; CDDP) in cervical carcinoma. Specifically, the therapeutic efficacy of combination of CDDP and E6/E7-specific siRNA was assessed in an in vivo cervical cancer xenograft models. The combination of CDDP and E6/E7-specific siRNA had greater efficacy than the combination of CDDP and E6-specific siRNA especially in terms of inducing cellular senescence. Through in vitro and in vivo experiments, the mechanism of synergy between these two treatments was revealed, demonstrating that the combination of E6/E7-specific siRNA and CDDP therapy was significantly superior to either modality alone. In vitro, long-term exposure of HeLa cells to the combination of CDDP and E6/E7-specific siRNA induced apoptosis and cellular senescence. In vivo, E6/E7-specific siRNA potentiated the antitumor efficacy of CDDP via induction of apoptosis, senescence and antiangiogenesis. Our results suggest that E6/E7-specific siRNA may be an effective sensitizer of CDDP chemotherapy in cervical cancer.
ISSN
0020-7136
Language
English
URI
https://hdl.handle.net/10371/78716
DOI
https://doi.org/10.1002/ijc.26197
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College of Pharmacy (약학대학)Dept. of Pharmacy (약학과)Journal Papers (저널논문_약학과)
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