COMBINED EFFECTS OF DELTA(7)-PROSTAGLANDIN A(1) AND LIPO DELTA(7)-PROSTAGLANDIN A(1) TO CIS-DIAMMINEDICHLOROPLATINUM(II) ON TUMOR-GROWTH INSCID MICE BEARING 2008-CELLS AND 2008 C13-CELLS/

The aim of this study was to elucidate effects of Delta(7)-prostagland in A(1) methyl ester (Delta(7)-PGA(1)) alone, and Delta 7-PGA(1) emuls ified in lecithin oil (lipo Delta(7)-PGA(1)) alone, and their combinat ions with cis-diamminedichloroplatinum(II) (CDDP) on the tumor growth of an ovarian carcinoma cell line resistant to CDDP (2008/c13) and the parental cell line (2008) in vitro and in scid mice. With regard to c oncentration of CDDP required for 50% inhibition of cell proliferation ill vitro (IC50), 2008/c13 was 5.76-fold higher resistant to CDDP tha n 2008, while the degree of resistance of 2008/c13 to Delta(7)-PGA(1) was less than a half of that to CDDP. When 2008 cells were heterotrans planted s.c. into the right flank of scid mice, the tumor growth was n ot inhibited by treatment with CDDP alone, Delta(7)-PGA(1) alone or li po Delta(7)-PGA(1) alone. However, when CDDP was combined with lipo De lta(7)-PGA(1) (but not Delta(7)-PGA(1)), the tumor growth was signific antly (P<0.05) inhibited on days 35 and 42 after tumor inoculation, co mpared to untreated and all alone treated groups. When CDDP-resistant 2008/c13 cells were inoculated s.c. into the right flank of scid mice, CDDP alone treatment resulted in a significant (P<0.05) inhibition of the tumor growth, suggesting that the sensitivity of this tumor to CD DP is rather higher than 2008-tumor of which growth was not inhibited by CDDP alone. A significant decrease of body weight was observed only when CDDP was combined with lipo Delta(7)-PGA(1) in scid mice bearing 2008 cells, as confirmed by monitoring hematocrit and body weight. Ho wever, these mice had no serious weight loss leading to death. These r esults suggest that combination of CDDP and lipo Delta(7)-PGA(1) may b e effective for treatment of patients with ovarian carcinoma clinicall y resistant or insensitive to CDDP.