Combination effect of anti-Fas antibody and chemotherapeutic drugs in ovarian cancer cells in vitro.

To clarify the significance of the Fas antigen (Ag) in gynecologic tumors, its expression in gynecologic cancer cell lines was examined. The Fas Ag was expressed in 6 of 15 cell lines. Five of 8 ovarian cancer cell lines but none of 4 choriocarcinoma cell lines expressed the Fas Ag. In drug-resistant cell lines derived from one of the Fas-positive cells, its expression was not lost after development of resistance to cisplatin, SN-38 or etoposide, but its expression was absent in the cell line resistant to Adriamycin. The effect of the anti-Fas antibody (Ab) was then studied. Apoptosis was induced in 7 of 9 Fas-positive cell lines, whereas the remaining two cell lines were unaffected. Furthermore, the combination effect of the anti-Fas Ab and drugs was examined in an ovarian cancer cell line and its drug-resistant variants, and a synergistic effect was observed. These results suggest important roles of the Fas Ag in ovarian cancer and the potential for overcoming drug resistance by a combination of the anti-Fas Ab and various drugs.