shRNA Depletion of cIAP1 Sensitizes Human Ovarian Cancer Cells to Anticancer Agent-Induced Apoptosis

Oncol Res. 2014;22(3):167-76. doi: 10.3727/096504015X14298122915664.

Abstract

Emerging evidence suggests a potential role of cellular inhibitor of apoptosis protein 1 (cIAP1) in the development of human ovarian cancer. However, its function in the progression of ovarian cancer has not been clearly determined. Our study aimed to investigate the effect of cIAP1 gene depletion on the chemosensitivity of ovarian cancer cells. We developed a novel short hairpin RNA (shRNA) plasmid specifically targeting cIAP1. Cell proliferation, invasion, and apoptosis of the shRNA-transfected cells were evaluated using MTT, Transwell chamber, and flow cytometric assays, respectively. The concentration of MMP-9 in the supernatant was detected by ELISA. Targeted depletion of cIAP1 by shRNA significantly reduced expression levels of cIAP1 mRNA and protein, leading to inhibition of cell proliferation and invasion capability in SKOV3 cells. At the same time, cIAP1 downregulation decreased the secretion of MMP-9. shRNA depletion of cIAP1 enhanced chemosensitivity of ovarian cancer cells to Taxol and carboplatin-induced apoptosis. cIAP1 is associated with tumor progression in human ovarian cancer. Therefore, cIAP1 might be a potential target for therapeutic anticancer drugs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / genetics
  • Carboplatin / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Inhibitor of Apoptosis Proteins / genetics*
  • Matrix Metalloproteinase 9 / metabolism
  • Neoplasm Invasiveness / genetics*
  • Neoplasm Invasiveness / pathology
  • Ovarian Neoplasms / drug therapy*
  • Ovarian Neoplasms / genetics
  • Paclitaxel / pharmacology
  • RNA Interference
  • RNA, Small Interfering

Substances

  • Antineoplastic Agents
  • Inhibitor of Apoptosis Proteins
  • RNA, Small Interfering
  • Carboplatin
  • MMP9 protein, human
  • Matrix Metalloproteinase 9
  • Paclitaxel