RADIOTHERAPY AS A CISPLATIN-SENSITIZER IN A RESISTANT OVARIAN-CARCINOMA CELL-LINE

BACKGROUND. Stage III ovarian carcinoma has shown resistance to adjuva nt chemotherapy following surgical cytoreduction. With recurrence of o varian carcinoma, cell lines may develop resistance to previously used chemotherapy. This contributes to the fact that survival rates for pa tients with ovarian carcinoma have not been dramatically improved in d ecades. The objective of this study is to evaluate radiotherapy as a c isplatin-sensitizer in a cisplatin-resistant ovarian carcinoma cell li ne. METHODS. In vitro OVCAR-3 human ovarian carcinoma cells were irrad iated with external beam radiation (XRT) at doses of 500, 1,500, and 4 ,500 centigray (cGy) in a single fractionation. Twelve hours after XRT , cells were treated with a dose of cisplatin for 2 hours (0, 1, 3, 9, 30, and 90 ug/mL). Cell attachment was determined by cell counts usin g a hemocytometer under phase-contrast microscopy. Analysis of varianc e followed by the Student Newman Keuls Test were used for statistical analysis. RESULTS. Dose-response curves demonstrate the results of thi s study as follows: (1) XRT has a significant direct effect on cell at tachment of OVCAR-3 cells in a dose-response relationship. (2) cisplat in has no effect on cell attachment in the absence of XRT. (3) When ce lls are exposed to XRT, cisplatin demonstrates a dose-response effect on cell attachment with a dose of XRT as low as 500 Gy. CONCLUSIONS. T his in vitro study suggests that XRT sensitizes cisplatin-resistant OV CAR-3 to cisplatin. This occurred with doses of radiation low enough t o suggest a potential clinical role in treating resistant ovarian carc inoma. (C) 1996 American Cancer Society.