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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
Author(s) -
Jung Hun Soon,
Erkin Ozgur Cem,
Kwon Mi Jeong,
Kim Seok Hyung,
Jung Jae In,
Oh YuKyoung,
Her Song Wook,
Ju Woong,
Choi YoonLa,
Song Sang Yong,
Kim Joong Kyu,
Kim Young Deug,
Shim Ga Yong,
Shin Young Kee
Publication year - 2011
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.26197
Subject(s) - in vivo , cisplatin , small interfering rna , hela , cancer research , chemosensitizer , in vitro , apoptosis , gene silencing , rna interference , cancer , cell culture , biology , pharmacology , chemistry , medicine , chemotherapy , rna , transfection , cytotoxicity , biochemistry , gene , genetics , microbiology and biotechnology
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.