Effect of shRNA targeting survivin on ovarian cancer

J Cancer Res Clin Oncol. 2012 Jul;138(7):1221-9. doi: 10.1007/s00432-012-1196-0. Epub 2012 Mar 18.

Abstract

Purpose: This study investigated the effect of shRNA targeting survivin on cultured ovarian cancer cells and on a murine ovarian cancer xenograft.

Methods: An RNAi plasmid for survivin was transfected into SKOV3 cells, and the effect of shRNA targeting survivin on the expression of survivin was determined. Transmission electron microscopy (TEM), flow cytometry, and TUNEL staining were used to assess apoptosis. The MTT assay was used to measure cell growth and changes in cisplatin sensitivity. SKOV3 cells were injected into nude mice, and the effect of shRNA targeting the survivin gene on tumor growth was assessed.

Results: SKOV3 cells transfected with an RNAi plasmid against survivin had increased apoptosis and slower growth. At the molecular level, these cells also had lower expression of survivin. Nude mice inoculated with SKOV3 cells developed cancers, and treatment with shRNA targeting survivin markedly inhibited the growth of these cancers with no obvious side effects.

Conclusions: Our studies of SKOV3 cells and ovarian cancer xenografts in nude mice indicate that shRNA targeting survivin has potential for the treatment of ovarian cancer.

MeSH terms

  • Animals
  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Inhibitor of Apoptosis Proteins / metabolism
  • Mice
  • Mice, Nude
  • Microscopy, Electron, Transmission
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • RNA Interference
  • RNA, Small Interfering / genetics*
  • Survivin
  • Transfection

Substances

  • Antineoplastic Agents
  • BIRC5 protein, human
  • Inhibitor of Apoptosis Proteins
  • RNA, Small Interfering
  • Survivin
  • Cisplatin