ANTITUMOR-ACTIVITY OF ZINOSTATIN STIMALAMER (YM881) IN HUMAN HEPATOMA-CELL LINES AND VX(2) LIVER TUMOR-BEARING RABBITS

Antitumor activities of zinostatin stimalamer (YM881) were examined in human hepatoma cell lines (SK-Hep1 and HuH2) and VX(2) liver tumor-be aring rabbits. YM881 inhibited the growth of human hepatoma cells in a dose-dependent manner. The IC50 values of YM881 causing a 50% inhibit ion of growth of SK-Hep1 and HuH2 cells were 6.7 and 27 nM, respective ly. In VX(2) tumor-bearing rabbits, administration of YM881 suspended in Lipiodol, an iodinated fatty acid ethylester of poppyseed oil, (YM8 81/Lipiodol suspension, 0.2 mg/0.2 ml/body) into the hepatic artery sh owed significant (p < 0.01, vs. sham-operated and Lipiodol-treated gro ups) inhibitory effects on tumor growth and histopathological changes at 1 and 2 weeks after administration. In contrast, Lipiodol (0.2 ml/b ody) tended to inhibit the growth of VX, tumor (p < 0.1, vs. sham-oper ated group) at 1 week after administration, but showed only moderate e ffects at 2 weeks after administration. Minimal necrosis was observed at 1 and 2 weeks after administration of Lipiodol, and histopathologic al findings were similar to those in the sham-operated group. From the present study, it is suggested that YM881/Lipiodol suspension showed antitumor activity in VX, tumor-bearing rabbits presumably due to the inhibition of the growth of hepatoma cells by YM881 itself. Lipiodol, on the other hand, is considered to augment the antitumor activity of YM881 by maintaining high YM881 concentrations in tumor tissue.