Radiotherapy as a cisplatin-sensitizer in a resistant ovarian carcinoma cell line

Abstract

Stage III ovarian carcinoma has shown resistance to adjuvant chemotherapy following surgical cytoreduction. With recurrence of ovarian carcinoma, cell lines may develop resistance to previously used chemotherapy. This contributes to the fact that survival rates for patients with ovarian carcinoma have not been dramatically improved in decades. The objective of this study is to evaluate radiotherapy as a cisplatin-sensitizer in a cisplatin-resistant ovarian carcinoma cell line. In vitro OVCAR-3 human ovarian carcinoma cells were irradiated 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, and 90 micrograms/mL). Cell attachment was determined by cell counts using a hemocytometer under phase-contrast microscopy. Analysis of variance followed by the Student Newman Keuls Test were used for statistical analysis. Dose-response curves demonstrate the results of this study as follows: (1) XRT has a significant direct effect on cell attachment of OVCAR-3 cells in a dose-response relationship. (2) cisplatin has no effect on cell attachment in the absence of XRT. (3) When cells are exposed to XRT, cisplatin demonstrates a dose-response effect on cell attachment with a dose of XRT as low as 500 Gy. This in vitro study suggests that XRT sensitizes cisplatin-resistant OVCAR-3 to cisplatin. This occurred with doses of radiation low enough to suggest a potential clinical role in treating resistant ovarian carcinoma.