EFFECT OF INTERFERON-GAMMA AND TUMOR-NECROSIS-FACTOR-ALPHA ON SENSITIVITY TO CISPLATIN IN OVARIAN-CARCINOMA CELL-LINES

This study aimed to investigate whether the biological response modifi ers (BRM) interferon gamma (IPN gamma) and tumour necrosis factor alph a (TNF alpha) could enhance the cytotoxic action of cisplatin on ovari an tumour cells in vitro. The sensitivity of four cell lines (OAW42, G G, JAM and PE01) to drugs and drug combinations was tested by a radiol abelled-thymidine incorporation assay. Cell lines demonstrated a range of sensitivity to cisplatin and the innate cytotoxic effect of each o f the BRM. When IFN gamma was used in combination with cisplatin, a si gnificant enhancement of cisplatin toxicity occurred in three of four cell lines. TNF alpha demonstrated such an effect in two cell lines bu t diminished the toxicity of cisplatin in one cell line. A purely addi tive effect of the agents may explain the enhanced toxicity of cisplat in in some of these cases. However, in one cell line at least (PE01), both TNF alpha and IFN gamma demonstrated a clearly synergistic effect with cisplatin. These BRM used in conjunction with cisplatin may prov ide better antitumour regimen than cisplatin alone in some patients wi th ovarian cancer, but the response is likely to be heterogeneous betw een patients.