Antitumor effect of GPA1734 in rat Walker 256 carcinoma.

Inhibition of angiogenesis offers an alternative approach to cancer chemotherapy, since solid tumor growth has an absolute dependency on angiogenesis. We have previously shown that 8,9-dihydroxy-7-methyl-benzo [b]quinolizinium bromide (GPA1734) is a basement membrane synthesis inhibitor, and that this compound acts as an antiangiogenic agent in the chick chorioallantoic membrane. When a piece of 10 mg from a Walker 256 carcinoma was implanted into the peritoneal cavity of rats, tumor grew to about 15 g within nine days after transplant. Daily treatment of Walker 256 carcinoma bearing animals with GPA1734, at doses 10-100 mg/kg intraperitoneally, restrained tumor growth in a dose dependent manner. Macroscopic examination showed tumor cells growing in spherical masses 5-8 mm in diameter, indicative of absence of neovascularization. GPA1734 at 300 microM had no direct effect on Walker 256 carcinoma cell culture growth. The antitumor effect of this agent on Walker 256 carcinoma may be related to its antiangiogenic properties.