Fas and Fas ligand expression and apoptosis in cisplatin-sensitive and -resistant human ovarian epithelial cancer cells.

Abstract

In the present study, we have used cultures of established cell lines of cisplatin (CDDP)-sensitive human ovarian epithelial tumours (OV2008 and A2780-s) and their resistant variants (C13* and A2780-cp, respectively) to assess the role of Fas/FasL system in the chemo-responsiveness of ovarian cancer cells to CDDP. CDDP was effective in inducing the expression of cell-associated Fas and FasL, sFasL and apoptosis in a concentration and time-dependent fashion in both OV2008 and A2780-s cell lines. In contrast, while CDDP was effective in increasing cell-associated Fas protein content in C13*, it failed to upregulate FasL and sFasL and induce apoptosis, irrespective of concentration and duration of CDDP treatment. In the resistant A2780-cp cells, neither Fas nor FasL upregulation and apoptosis were evident in the presence of CDDP. Addition of concentrated spent media from OV2008 after CDDP on C13* cells demonstrates a low level of apoptotic activity which is partially blocked by a Fas antagonistic Ab. Activation of the Fas signaling pathway, by addition to the cultures an agonistic Fas mAb, was effective in inducing apoptosis in both OV2008 and C13*. A significant interaction between CDDP and Fas agonist mAb was observed in the apoptotic response in OV2008 and C13* when cultured in the presence of both agents. (Abstract shortened by UMI.)