Growth-inhibitory signals by activin A do not affect anticancer drug-sensitivity and acquired multi-drug-resistance in human ovarian endometrioid adenocarcinoma OVK-18 cells

Abstract

Using the human ovarian adenocarcinoma cell line, OVK-18, which is sensitive to activin A-mediated inhibition of growth and various anticancer drugs, we determined whether activin A altered the sensitivity of these cells to seven anticancer drugs. The relationship between the sensitivity to activin and the resistance to anticancer drugs was also investigated in OVK-18 parent cells and OVK-18-derived CDDP-resistant cells. Activin A inhibited proliferation of OVK-18 parent cells in a dose-dependent manner, although it did not affect the sensitivity of OVK-18 parent cells to the seven anticancer drugs, CDDP, CBDCA, adriamycin, paclitaxel, SN38, terarubicin and etoposide (VP16). Both the sensitivity to activin A-mediated inhibition of growth and the sensitivity to anticancer drug-induced apoptosis were reduced in CDDP-resistant cells, while their sensitivity to the seven anticancer drugs was not affected by activin A. Flow cytometric analysis revealed a significant reduction in type IIA activin receptor expression on the surface of CDDP-resistant cells. These results indicate that the activin A-induced intracellular signals inhibiting cell growth are independent of the inhibition caused by the seven anticancer drugs, and suggest that the reduced sensitivity of CDDP-resistant cells to activin A is derived in part from reduced activin receptor expression and not acquired drug-resistance.