Bcl-X(L) is functionally non-equivalent for the regulation of growth and survival in human ovarian cancer cells

Gynecol Oncol. 2006 Feb;100(2):254-63. doi: 10.1016/j.ygyno.2005.08.028. Epub 2005 Sep 26.

Abstract

Objective: To investigate the role of Bcl-X(L) on the growth and survival of human ovarian carcinoma cells.

Methods: In this study, we enforced down-regulation of Bcl-X(L) by RNA interference in ovarian carcinoma cell lines CaOV3, SKOV3ip1 and OVCAR3 cell lines expressing various levels of Bcl-X(L). We also established stable transfectants of OVCAR3 cells overexpressing Bcl-X(L). We recently showed that Bcl-2 regulates cell cycle progression in ovarian cancer cells. Thus, the effect of Bcl-X(L) modulation on the rate of cell growth was determined by XTT assay. To evaluate the role of Bcl-X(L) in drug-induced apoptosis, cisplatin- and paclitaxel-induced apoptosis were determined in vitro for each of the three cell lines. Ovarian tumor cells must acquire the ability to survive in non-adherent conditions to grow in ascetic fluids. To mimic loss of anchorage and investigate the role of Bcl-X(L) in this process, cells were cultured on Hydrogel-coated plates and nuclear fragmentation, caspase-3 activation and nuclear propidium iodide staining were used to determine apoptosis.

Results: We show that enforced down-regulation of Bcl-X(L) protein significantly affected the growth rates of CaOV3 whereas it had only minimal effect on the other two cell lines. Down-regulation of Bcl-X(L) enhanced the sensitivity of CaOV3, OVCAR3 and SKOV3ip1 to cisplatin and paclitaxel. The susceptibility to apoptosis induced by loss of anchorage was also increased but in a cell line-dependent manner. Overexpression of Bcl-X(L) slowed the growth of OVCAR3 cells and conferred resistance to drug-induced apoptosis and apoptosis induced by loss of anchorage.

Conclusion: Altogether, these findings demonstrate that modulation of Bcl-X(L) provokes changes in ovarian cancer cell growth and survival that are cell line-specific. Consequently, therapeutic strategy for treatment of ovarian cancer that target Bcl-X(L) will likely yield variable responses.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Cell Adhesion / physiology
  • Cell Growth Processes
  • Cell Line, Tumor
  • Cell Survival / physiology
  • Cisplatin / pharmacology
  • Female
  • Humans
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Paclitaxel / pharmacology
  • RNA, Small Interfering / genetics
  • Transfection
  • bcl-X Protein / antagonists & inhibitors
  • bcl-X Protein / biosynthesis
  • bcl-X Protein / genetics
  • bcl-X Protein / physiology*

Substances

  • BCL2L1 protein, human
  • RNA, Small Interfering
  • bcl-X Protein
  • Paclitaxel
  • Cisplatin