The effect of Amifostine on the in vitro cytotoxicity of chemotherapeutic agents in three epithelial ovarian carcinoma cell lines

Abstract

Objectives. Amifostine protects against a spectrum of toxicities induced by chemotherapy without affecting tumor cell kill. This is supported by clinical data and in vivo animal studies. However, there is a paucity of data on its effect on the tumor cytotoxicity of several chemotherapeutic agents used in recurrent epithelial ovarian cancer. This study compares in vitro cytotoxicity before and after addition of amifostine. Methods. Three epithelial ovarian carcinoma cell lines (SKOV3, 420, 429) were exposed to cis-platinum, paclitaxel, doxorubicin, etoposide, 5-fluorouracil, bleomycin, 4-epidoxorubicin, 4-HC (activated cyclophosphamide), vincristine, actinomycin D, mitomycin C, and topotecan. Cells were pretreated with either 0 or 1.2 mM amifostine. Tumor cell kill after 6 days of incubation was measured using the ATP cell viability assay. Paired samples Student's t statistic was used to test the difference in mean ATP levels between drug-treated samples with and without pretreatment with amifostine. Results. SKOV3 was sensitive to paclitaxel, actinomycin D, 4-epidoxorubicin, and vincristine. Cell line 420 was sensitive to paclitaxel, etoposide, and 5-fluorouracil. Cell line 429 was sensitive to paclitaxel and 5-fluorouracil. There was no significant difference in the mean ATP levels between drug-treated samples with and without pretreatment with amifostine for each of the sensitive drugs in all three cell lines. Similarly, there was no significant difference in the mean ATP levels in cis-platinum and 4-HC treated samples with and without pretreatment with amifostine. Conclusions. These results show that at the cellular level amifostine did not protect epithelial ovarian carcinoma cells against tumor cell kill.