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

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.

journal_name

Gynecol Oncol

journal_title

Gynecologic oncology

authors

Dodier P,Piché A

doi

10.1016/j.ygyno.2005.08.028

subject

Has Abstract

pub_date

2006-02-01 00:00:00

pages

254-63

issue

eissn

0090-8258

issn

1095-6859

pii

S0090-8258(05)00725-0

journal_volume

100

pub_type

杂志文章

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