Resistance to cisplatin does not affect sensitivity of human ovarian cancer cell lines to mifepristone cytotoxicity

<p>Abstract</p> <p>Background</p> <p>The prototypical antiprogestin mifepristone exhibits potent growth inhibition activity towards ovarian cancer cells <it>in vitro </it>and <it>in vivo</it>. The aim of this research was to establish whether mifepristone is capable of inhibiting cell proliferation and inducing apoptotic cell death regardless of the degree of sensitivity ovarian cancer cells exhibit to cisplatin.</p> <p>Methods</p> <p>OV2008, OV2008/C13, A2780, A2780/CP70, Caov-3, and SK-OV-3 cell lines exhibiting a range of sensitivities to cisplatin were used. Growth inhibition, cell viability, and sub-diploid DNA content in response to treatment with escalating doses of either mifepristone or cisplatin were assessed by microcapillary cytometry. Apoptotic cell death was evaluated by measuring genomic DNA fragmentation and cleavage of caspase-3 and poly (ADP ribose) polymerase (PARP).</p> <p>Results</p> <p>The sensitivities to cisplatin manifested by the cell lines were OV2008 > A2780 > Caov-3 > SK-OV-3 > OV2008/C13 > A2780/CP70. Mifepristone inhibited the growth of all six cell lines in a dose-related manner with IC_50sranging from ~6–12 μM and without significant correlation with the relative sensitivities the cells displayed for cisplatin. Moreover, at the highest concentration studied, mifepristone triggered apoptotic death in all six cell lines as evidenced by the increase in sub-diploid fragmented DNA content and cleavage of caspase-3 and of its downstream substrate PARP.</p> <p>Conclusion</p> <p>Mifepristone is cytotoxic towards ovarian cancer cells independent of the sensitivity exhibited by the cells to cisplatin, displaying cytostatic effects at lower concentrations and lethal effects at higher concentrations. Mifepristone monotherapy emerges as a valuable therapeutic alternative for platinum-resistant ovarian cancers.</p>

Abstract licence: CC BY-NC-ND

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.