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Use of Interferon-γ Enzyme-linked Immunospot Assay to Characterize Novel T-cell Epitopes of Human Papillomavirus
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Down-regulation of HPV18 E6, E7, or VEGF expression attenuates malignant biological behavior of human cervical cancer

Li Chen1, Yuan-Yuan Wu, Peigen Liu

  • 1Department of Pathology, Nantong University School of Medicine, 226001 Nantong, China. bl1@ntu.edu.cn

Medical Oncology (Northwood, London, England)
|January 12, 2011
PubMed

Insights

RNA interference targeting human papillomavirus type 18 E6/E7 and vascular endothelial growth factor effectively suppresses cervical cancer cell growth and malignant behaviors. This RNA interference strategy shows promise for treating cervical cancer.

Area of Science:

  • Oncology
  • Molecular Biology
  • Virology

Background:

  • Cervical cancer is frequently associated with persistent infection by high-risk human papillomavirus (HPV), particularly HPV type 18.
  • Vascular Endothelial Growth Factor (VEGF) plays a critical role in tumor angiogenesis and progression.
  • HPV18 E6 and E7 oncoproteins are key drivers of cervical carcinogenesis.

Purpose of the Study:

  • To investigate the therapeutic potential of down-regulating HPV18 E6/E7 and VEGF using RNA interference in cervical cancer cells.
  • To assess the impact of this down-regulation on cancer cell proliferation, apoptosis, migration, invasion, and adhesion.

Main Methods:

  • Construction and transfection of recombinant plasmids encoding short hairpin RNA (shRNA) targeting HPV18 E6, E7, and VEGF into HeLa cervical cancer cells.
  • Evaluation of mRNA and protein expression levels post-transfection.
  • Assessment of cellular proliferation, apoptosis, migration, invasion, and adhesion in vitro.
  • Establishment of a xenograft tumor model in nude mice to evaluate in vivo efficacy.

Main Results:

  • Transfection significantly reduced E6, E7, and VEGF mRNA levels, as well as VEGF protein expression.
  • Down-regulation of HPV18 E6/E7 and VEGF increased apoptosis and decreased proliferation, invasion, and adhesion of HeLa cells.
  • In vivo studies demonstrated significant inhibition of xenograft tumor growth.

Conclusions:

  • RNA interference is an effective method to suppress HPV18 E6/E7 and VEGF expression in human cervical cancer cells.
  • Suppression of these targets attenuates the malignant biological behavior of cervical cancer cells.
  • Targeting HPV E6/E7 or VEGF expression via RNA interference represents a promising anti-cervical cancer strategy.

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