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

Hun Soon Jung, Ozgur Cem Erkin, Mi Jeong Kwon, Seok Hyung Kim, Jae In Jung, Yu Kyoung Oh, Song Wook Her, Woong Ju, Yoon La Choi, Sang Yong Song, Joong Kyu Kim, Young Deug Kim, Ga Yong Shim, Young Kee Shin

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

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.

Original languageEnglish
Pages (from-to)1925-1936
Number of pages12
JournalInternational Journal of Cancer
Volume130
Issue number8
DOIs
StatePublished - 15 Apr 2012

Keywords

  • HPV E6/E7 siRNA
  • cervical carcinoma
  • chemosensitizer
  • cisplatin (CDDP) chemotherapy
  • human papillomavirus

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