Prostaglandins (PGs) with antiproliferative activity against tumor cells consist of the cyclopentenone PGs and the alkylidene cyclopentenone PGs. Such PGs are PGD2, PGJ2, delta 12-PGJ2, PGA1, delta 7-PGA1, and PGA2. Both PGJ2 and delta 12-PGJ2 are ultimate metabolites of PGD2 and have potent antiproliferative activity on tumor cells. delta 12-PGJ2 was identified in human urine, whereas delta 7-PGA1 has not been found in the human body. One important characteristic of both delta 7-PGA1 and delta 12-PGJ2 is that they have little cross resistance with cisplatin and adriamycin in vitro and in vivo. delta 7-PGA1 has 5-fold greater antitumor activity than delta 12-PGJ2. Methyl ester-delta 7PGA1 (methyl-delta 7-PGA1) is stable chemically and can be easily synthesized in large amounts. All four isomers of methyl-delta 7-PGA1 showed the same antiproliferative activities on ovarian carcinoma cells. In addition, methyl-delta 7-PGA1 integrated in lipid microspheres (lipo-methyl-delta 7-PGA1) is more soluble in water than methyl-delta 7-PGA1 alone. Hence, lipo-methyl-delta 7-PGA1 was selected for extensive preclinical studies. Intravenous administration of lipo-methyl-delta 7-PGA1 could inhibit the growth of both HeLa S3 and Lovo colon cancer cells transplanted subcutaneously in nude mice. Lipo-methyl-delta 7-PGA1 by intraperitoneal administration could prolong the survival of scid mice bearing 2008C/13* cells resistant to cisplatin. The combined administration of cisplatin and lipo-methyl-delta 7-PGA1 prolonged the survival of nude mice bearing HRA cells compared with each single agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)