Interaction of interferon gamma and CPT-11, a new derivative of camptothecin, in human endometrial carcinoma cell lines.

Abstract

The anti-proliferative effects of interferon gamma (IFN-gamma) and CPT-11, a new derivative of camptothecin, both singly and in combination, on two human endometrial carcinoma cell lines, HHUA and ISHIKAWA, were examined in vitro. The HHUA cells were responsive dose-dependently to IFN-gamma, while the ISHIKAWA cells were unresponsive to IFN-gamma. Both cell lines were responsive dose-dependently to CPT-11. In both cell lines, IFN-gamma at clinically achievable concentrations (10 and 100 U ml-1 enhanced the anti-proliferative activity of CPT-11 in the range of concentrations where CPT-11 showed more than 10% cell growth inhibition. Sequential treatment with CPT-11 followed by incubation with IFN-gamma resulted in significant cell growth inhibition, but not vice versa. Flow cytometric studies indicated that the combined anti-proliferative effect did not correlate with cytokinetic alterations. Treatment with IFN-gamma did not change the extractable topoisomerase I activity of the HHUA and ISHIKAWA cells. The combination therapy of IFN-gamma and CPT-11 could provide a new approach against endometrial cancer.