[Anti-tumor activity of zinostatin stimalamer (YM 881) examined by human hepatoma cells in vitro and VX2 liver tumor in vivo].
Anti-tumor activities of zinostatin stimalamer (YM 881) were examined using human hepatoma cell lines (SK-Hep1 and HuH 2) and VX2 liver tumor-bearing rabbits. YM881 inhibited the growth of human hepatoma cells in a dose-dependent manner. The IC50 values of YM881 against SK-Hep 1 and HuH 2 cells were 6.7 and 27 mM, respectively. In VX2 tumor-bearing rabbits, administration of YM 881 suspended in iodinated fatty acid ethylesters of poppyseed oil (YM 881/Lipiodol suspension, 0.2 mg/0.2 ml/body) into the hepatic artery showed significant (p < 0.01, vs sham-operated and Lipiodol-treated groups) inhibitory effects on the growth and pathological changes 1 and 2 weeks after administration. On the other hand, Lipiodol (0.2 ml/body) showed a tendency to inhibit the growth of VX2 tumor (p < 0.1, vs sham-operated group) 1 week after administration, but it showed only moderate effects on the VX2 tumor growth 2 weeks after administration. Minimal necrosis was observed 1 and 2 weeks after administration of Lipiodol, and these pathological findings were similar to those in the sham-operated group. From the present study, it is suggested that YM 881/Lipiodol suspension showed the anti-tumor activity against VX2 tumor-bearing rabbits, presumably due to the inhibition of the growth of hepatoma cell by YM 881 per se. On the other hand, Lipiodol is considered to augment the anti-tumor activity by maintaining high YM881 concentrations in tumor tissue.
Tanaka
S
S
Pharmacology Dept., Clinical Pharmacology Res. Lab., Kumamoto University Medical School.
Fujihara
A
A
Yamamoto
M
M
Asano
M
M
Ida
H
H
Ohmi
Y
Y
Kitazaki
T
T
Kikuchi
Y
Y
Yoshida
S
S
Okamiya
H
H
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D006499:Hepatic Artery; D006801:Humans; D007261:Infusions, Intra-Arterial; D007459:Iodized Oil / Q000008:administration & dosage*; D008113:Liver Neoplasms / Q000473:pathology*; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D011817:Rabbits; D014407:Tumor Cells, Cultured / Q000187:drug effects; D009353:Zinostatin / Q000008:administration & dosage* / Q000494:pharmacology
D007459:Iodized Oil; D009353:Zinostatin