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Anticancer Effects of Free Polyunsaturated Fatty Acids in an Oily Lymphographic Agent following Intrahepatic Arterial Administration to a Rabbit Bearing VX-2 Tumor

Department of Pharmacy, Kumamoto University Hospital [Y. H., S. F., S. K., M. Na.], 1-1-1 Honjo, Kumamoto 860; Department of Pharmaceutical Sciences, Josai University [T. K.], 1-1 Keyakidai, Sakado, Saitama 350-02; Department of Antibiotics, National Institute of Health [M. Nu.] 2-10-35 Kamiosaki, Shinagawa-ku, Tokyo 141; and Tsukuba Research Laboratory, Nippon Oil and Fats Co. [Y. I., J. H.], 5-10 Tokodai, Toyosato-machi, Tsukuba, Ibaraki 300-26, Japan

The anti-hepatic cancer effects of three free polyunsaturated fatty acids (linoleic, -linolenic, and -linolenic acids) dissolved in an oily lymphographic agent, Lipiodol Ultra-Fluid (Lipiodol), following intrahepatic arterial administration were examined using a rabbit liver cancer model, VX-2. The tumor was inoculated into the subcapsular parenchyma of the liver of rabbits, and Lipiodol alone or Lipiodol containing each one of the free fatty acids was administered into the hepatic artery 14 days after inoculation. The rabbits were sacrificed 7 days after administration. Lipiodol containing one of the fatty acids selectively remained in the tumor area. Although VX-2 tumor grew extensively in both the untreated group and the group that received Lipiodol alone, growth of VX-2 tumor was greatly suppressed in the group that received Lipiodol containing the free fatty acid. Pathological observation also showed that Lipiodol containing the free fatty acid had an anticancer effect on VX-2 tumor growing in the liver of rabbits. Average survival days in the group treated with Lipiodol containing -linolenic acid were significantly prolonged compared with those in the control groups. Although growth rates of the tumor at the death of rabbits were large in the control groups, VX-2 tumor shrank at death of five rabbits of six in the group treated with Lipiodol containing -linolenic acid.

These results suggest that the intrahepatic arterial administration of Lipiodol containing the free fatty acids is an effective method of delivery of these fatty acids as anticancer agents.

¹ To whom requests for reprints should be addressed.

Received 2/12/90. Accepted 10/31/91.