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In vitro and in vivo growth suppression of HPV-related cancer cells by siRNA targeting E6 oncogene

Research Project

Project/Area Number 15591991
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Pathobiological dentistry/Dental radiology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

YAMATO Kenji  Tokyo Medical and Dental University, Graduate School, Division of Oral Health Science, Lecturer, 大学院・医歯学総合研究科, 講師 (50174751)

Co-Investigator(Kenkyū-buntansha) YAMADA Taketo  Keio University, School of Medicine, Lecturer, 医学部, 講師 (60230463)
Project Period (FY) 2003 – 2004
Project Status Completed (Fiscal Year 2004)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsHPV / E6 / RNAi / siRNA / growth / HPV / p53 / Rb / siRN / in vivo
Research Abstract

Human papillomavirus (HPV) types 16 and 18, causative agents of cervical cancers, encode the E6 and E7 oncogenes, whose simultaneous expression is pivotal for the malignant transformation and maintenance of malignant phenotypes. In the hope of developing a gene-specific therapy for HPV-related cancer, we examined the effects of E6 short-interfering RNA (siRNA) on the expression of these oncogenes and cell growth of HPV-related cervical cancer cells. Using SiHa cervical cancer cells, we demonstrated that HPV16 E6 siRNA decreased the levels of mRNA coding E6 as well as that coding E7 protein, and also induced nuclear accumulation of p53, the most important target of E6. E6 siRNA suppressed monolayer and anchorage-independent growth of SiHa cells, which was associated with p21^<CIP1/WAF1> induction and hypophosphorylation of retinoblastoma protein (Rb). Further, SiHa cells treated with E6 siRNA formed tumors in NOD/SCID mice that were significantly smaller than in those treated with control siRNA.
we also found 2 types of siRNAs targeting HPV18 E6 which exerted a negative growth effect on HPV18-positive cervical cancer cells (HeLa and SW756), in part, inducing cell death. One siRNA (Ex-18E6) knocked down both E6 and E7 expression. The other (Sp-18E6) suppressed E6 to a similar level as Ex-18E6, however, less efficiently inhibited E7 as compared to Ex-18E6. Although both siRNAs induced cell death, Sp-18E6 siRNA induced more prominent cell death than Ex-18E6, suggesting that selective knock-down of E6 might be superior to simultaneous knock-down of E6 and E7 for the siRNA therapy of cervical cancer.
Our results show HPV E6 siRNA as a candidate for gene-specific therapy for HPV-related cervical cancer.

Report

(3 results)
  • 2004 Annual Research Report   Final Research Report Summary
  • 2003 Annual Research Report
  • Research Products

    (16 results)

All 2004 2003 Other

All Journal Article (13 results) Publications (3 results)

  • [Journal Article] Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress : implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species.2004

    • Author(s)
      Ito, K.et al.
    • Journal Title

      Cancer Res. 64

      Pages: 1071-1078

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of apoptosis in human myeloid leukemia cells by 1'-acetoxychavicol acetate (ACA) through a mitochondrial- and Fas-mediated dual mechanisum.2004

    • Author(s)
      Ito, K.et al.
    • Journal Title

      Clinical Cancer Res. 10

      Pages: 2120-2030

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Eradication of HPV post-surgical treatments, its correlation with specific types, types of surgery and the physical status.2004

    • Author(s)
      Fen, J.et al.
    • Journal Title

      Oncol Rep. 12

      Pages: 375-379

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress : implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species.2004

    • Author(s)
      Ito, K., Nakazato, T., Yamato, K., Miyakawa, Y., Yamada, T.,, Hozumi, N., Segawa, K., Ikeda, Y., Kizaki, M.
    • Journal Title

      Cancer Res. 64

      Pages: 1071-1078

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of apoptosis in human myeloid leukemia cells by 1'-acetoxychavicol acetate (ACA) through a mitochondrial-and Fas-mediated dual mechanism.2004

    • Author(s)
      Ito, K., Nakazawa, T., Murakami, A., Yamato, K., Miyakawa, Y., Yamada, T., Hozumi, N., Ohigashi, H., Ikeda, Y., Kizaki, M.
    • Journal Title

      Clinical Cancer Res. 10

      Pages: 2120-2130

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Eradication of HPV post-surgical treatments, its correlation with specific types, types of surgery and the physical status.2004

    • Author(s)
      Fen, J., Yoshinouchi, M., Nakamura.K., Kodama, J., Nasu, Y., Yamato, K., Hiramatsu, Y.
    • Journal Title

      Oncol.Rep. 12

      Pages: 375-379

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress : implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species.2004

    • Author(s)
      Ito, K., et al.
    • Journal Title

      Cancer Res. 64

      Pages: 1071-1078

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Induction of apoptosis in human myeloid leukemia cells by 1'-acetoxychavicol acetate (ACA) through a mitochondrial- and Fas-mediated dual mechanism.2004

    • Author(s)
      Ito, K., et al.
    • Journal Title

      Clinical Cancer Res. 10

      Pages: 2120-2130

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Eradication of HPV post-surgical treatments, its correlation with specific types, types of surgery and the physical status2004

    • Author(s)
      Fen, J., et al.
    • Journal Title

      Oncol Rep. 12

      Pages: 375-379

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Caffeine induces G2/M arrest and apoptosis via novel p53-dependent pathway in NB4 promonocytic leukemia cells.2003

    • Author(s)
      Ito, K.et al.
    • Journal Title

      J.Cell Physiol. 196

      Pages: 276-283

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vitro and in vivo growth suppression of human papillomavirus (HPV)16-positive cervical cancer cells by E6 siRNA.2003

    • Author(s)
      Yoshinouchi, M. et al.
    • Journal Title

      Mol.Ther. 8

      Pages: 762-768

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] Caffeine induces G2/M arrest and apoptosis via novel p53-dependent pathway in NB4 promonocytic leukemia cells.2003

    • Author(s)
      Ito, K., Nakazoto, T., Miyakawa, Y., Yamato, K., Ikeda, Y., Kizaki, M.
    • Journal Title

      J.cell.Physiol. 196

      Pages: 276-283

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Journal Article] In vitro and in vivo growth suppression of human papillomavirus (HPV)16-positive cervical cancer cells by E6 siRNA.2003

    • Author(s)
      Yoshinouchi, M., Yamada, T., Kizaki, M., Fen, J., Koseki, T., Ikeda, Y., Nishihara, T., Yamato, K.
    • Journal Title

      Mol.Ther. 8

      Pages: 762-768

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2004 Final Research Report Summary
  • [Publications] Ito, K.et al.: "Caffeine induces G2/M arrest and apoptosis via novel p53-dependent pathway in NB4 promonocytic leukemia cells."J.Cell Physiol.. 196. 276-283 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Yoshinouchi, M. et al.: "In vitro and in vivo growth suppression of human papillomavirus (HPV)16-positive cervical cancer cells by E6 siRNA."Mol.Ther.. 8. 762-768 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ito, K.et al.: "Induction of apoptosis in leukemic cells by homovanillic acid derivative, capsaicin, through oxidative stress : implication of phosphorylation of p53 at Ser-15 residue by reactive oxygen species."Cancer Res.. 64. 1071-1078 (2004)

    • Related Report
      2003 Annual Research Report

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Published: 2003-04-01   Modified: 2016-04-21  

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