S. Yokoyama et al., Suppression of rat liver tumorigenesis by 25-hydroxycholesterol and all-trans retinoic acid: Differentiation therapy for hepatocellular carcinoma, INT J ONCOL, 15(3), 1999, pp. 565-569
To determine whether differentiation therapy is useful in treating patients
with hepatoma, we assayed the effects of 25-hydroxycholesterol (25-OH) and
/or all-trans retinoic acid (ATRA) on rat AH136B ascites hepatoma cells. Fl
ow cytometric DNA analysis showed that treatment of cells with 25-OH alone
induced entry into the sub-G1 phase in a dose-dependent manner. While ATRA
alone was ineffective, it enhanced the activity of 25-OH. Condensed and fra
gmented nuclei occurred mainly in cells treated with 25-OH (4 mu g/ml). Whe
n cells treated with 25-OH (4 mu g/ml), or 25-OH (4 mu g/ml) + ATRA (1 mu M
) were transplanted into Donryu rats, we found that tumor development was c
ompletely inhibited; in contrast, rats administered the methanol-treated AH
136B cells developed tumors. These findings suggest that AH136B cells in th
e sub-G1 phase can not recover tumorigenicity, and that the administration
of a 3-hydroxy-3-methylglutaryl CoA. reductase inhibitor, such as 25-OH, an
d ATRA may be effective in treating patients with hepatoma.