EFFECTS OF DELTA(7)-PROSTAGLANDIN A(1) METHYL-ESTER ON HUMAN OVARIAN-CANCER CELL-GROWTH IN-VITRO AND IN NUDE-MICE

Abstract

The antitumor activities of Delta(7)-prostaglandin A(1) methyl ester (Delta(7)-PGA(1)) and Delta(7)-PGA(1) emulsified in lecithin oil (lipo Delta(7)-PGA(1)) were studied in nude mice models with ascites or solid tumors formed by i.p. or s.c. inoculation of human ovarian cancer cells (HRA). Inhibitory effects of Delta(7)-PGA(1), on the HRA cell proliferation in vitro were about 3.8-fold higher than those of lipo Delta(7)-PGA(1). In the ascites tumor model, the median survival in a CDDP alone treated group among alone treated groups was longest and followed by a Delta(7)-PGA(1) alone treated group. A combination of CDDP and Delta(7)-PGA(1) resulted in a significant (p<0.05) prolongation of the median survival, compared to that in any alone treated group, while even when CDDP was combined with lipo Delta(7)-PGA(1) the survival was not improved, compared to that in a CDDP alone treated group. In addition, analyses of the survival curve revealed that a combination of CDDP with Delta(7)-PGA(1) resulted in higher survival rate than with lipo Delta(7)-PGA(1). On the other hand, in the s.c. tumor model lipo Delta(7)-PGA(1) (but not Delta(7)-PGA(1)) significantly (p<0.05) inhibited the tumor growth. When combining lipo Delta(7)-PGA(1) with CDDP, its inhibitory effect was further enhanced. Subsequently, the survival time in a lipo Delta(7)-PGA(1)+CDDP treated group was longest and 3 out of 9 mice survived more than 100 days. Taken together, we conclude that Delta(7)-PGA(1) might be suitable for local treatment in i.p, ascites tumors while lipo Delta(7)-PGA(1) is useful for remote treatment in s.c. solid tumors.