Preliminary study of the effects of vitamin A on antineoplastic activities of chemotherapeutic agents in glioma.

Abstract

The effects of retinoids on the growth of murine and human gliomas and on the antineoplastic activities of 1-(4-amino-2-methyl-5-pyrimidinyl)methyl-3-(2-chloroethyl)-3-nitrosourea hydrochloride (ACNU) and vincristine were studied. No significant inhibitory effect on proliferation of human glioblastoma (GB) cells in vitro was found 48 hours after administration of 0.003 mg/ml of retinol acetate. No significant inhibition of murine glioma growth nor significant prolongation of median survival was observed when 70 mg/kg of retinol palmitate was given every other day 5 times from day 7 after the subcutaneous inoculation of glioma. Significant inhibition of GB cell proliferation by ACNU and vincristine in vitro was dose-dependent. The antitumor effects of ACNU and vincristine in vitro were usually enhanced by 0.003 mg/ml of retinol acetate and a statistically significant enhancing effect was found in 10-6 g/ml of ACNU. The inhibition of tumor growth in vivo induced by ACNU given every other day 5 times was usually enhanced by the addition of 70 mg/kg of retinol palmitate given 4 hours prior to each ACNU administration, and its statistical significance was found on day 21 in treatment with 1 mg/kg of ACNU and on days 21 and 28 in treatment with 10 mg/kg of ACNU. The increase in median survival induced by ACNU administration was also enhanced by treatment with retinol palmitate, but no statistical significance of enhancement was found. In addition, the percentage cure of subcutaneous glioma was higher in treatment with ACNU plus retinol palmitate than with ACNU alone.