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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

Title
The synergistic therapeutic effect of cisplatin with Human papillomavirus E6/E7 short interfering RNA on cervical cancer cell lines in vitro and in vivo
Authors
Jung H.S.Erkin O.C.Kwon M.J.Kim S.H.Jung J.I.Oh Y.-K.Her S.W.Ju W.Choi Y.-L.Song S.Y.Kim J.K.Kim Y.D.Shim G.Y.Shin Y.K.
Ewha Authors
주웅
SCOPUS Author ID
주웅scopus
Issue Date
2012
Journal Title
International Journal of Cancer
ISSN
0020-7136JCR Link
Citation
vol. 130, no. 8, pp. 1925 - 1936
Indexed
SCI; SCIE; SCOPUS WOS scopus
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. © 2011 UICC.
DOI
10.1002/ijc.26197
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의학전문대학원 > 의학과 > Journal papers
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