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Antitumor Activity of 13,14-Dihydro-15-deoxy-⁷-prostaglandin-A₁-methyl Ester Integrated into Lipid Microspheres against Human Ovarian Carcinoma Cells Resistant to Cisplatin in Vivo¹

Department of Obstetrics and Gynecology, The Jikei University School of Medicine, Minato-ku, Tokyo 105-8461 [H. S., S. N., T. T.]; Department of Obstetrics and Gynecology, Shiga University of Medical Science, Ohtu 520-21 [M. A.]; Department of Pharmacology, Kobe Gakuin University, Kobe 651-2113 [A. H., S. K., S. F.]; and Department of Internal Medicine, Aichi Cancer Center, Nagoya 464-0021 [M. F.], Japan

One of the ⁷-prostaglandin A₁ derivatives with unique antitumor activities, 13,14-dihydro-15-deoxy-⁷-prostaglandin-A₁-methyl ester, was integrated into lipid microspheres (Lipo-TEI9826) and examined for its antitumor effect in vitro and in vivo. The in vitro relative resistance of human ovarian cancer, A2780^CP, to cisplatin (CDDP) and Lipo-TEI9826 was 27.3 and 2.0, respectively, compared with A2780, the parent cell line of A2780^CP. In in vivo experiments, when A2780^CP and the parent cell line A2780 were inoculated into nude mice, A2780^CP grew two times more rapidly than did A2780. The growth of A2780^CP tumor was not suppressed by CDDP, whereas that of the A2780 tumor was significantly suppressed. Nevertheless, the growth of both the A2780 and the A2780^CP inoculated tumors was significantly inhibited by treatment with Lipo-TEI9826 at any time after the initial treatment, compared with the lipid microspheres only. These results show that Lipo-TEI9826 may be an effective antitumor agent and capable of overcoming CDDP resistance.

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