Combined effects of Delta(7)-prostaglandin A(1) and lipo Delta(7)-prostaglandin A(1) to cis-diamminedichloroplatinum(II) on tumor growth in scid mice bearing 2008 and 2008/c13 cells

The aim of this study was to elucidate effects of Delta(7)-prostaglandin A(1) methyl ester (Delta(7)-PGA(1)) alone, and Delta 7-PGA(1) emulsified in lecithin oil (lipo Delta(7)-PGA(1)) alone, and their combinations 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 concentration of CDDP required for 50% inhibition of cell proliferation in vitro (IC50), 2008/c13 was 5.76-fold higher resistant to CDDP than 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 heterotransplanted s.c. into the right flank of scid mice, the tumor growth was not inhibited by treatment with CDDP alone, Delta(7)-PGA(1) alone or lipo Delta(7)-PGA(1) alone. However, when CDDP was combined with lipo Delta(7)-PGA(1) (but not Delta(7)-PGA(1)), the tumor growth was significantly (P<0.05) inhibited on days 35 and 42 after tumor inoculation, compared 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 CDDP 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. However, these mice had no serious weight loss leading to death. These results suggest that combination of CDDP and lipo Delta(7)-PGA(1) may be effective for treatment of patients with ovarian carcinoma clinically resistant or insensitive to CDDP.