THE INHIBITORY EFFECT OF THE COMBINATION OF ANTINEOPLASTON A-10 INJECTION WITH A SMALL DOSE OF CIS-DIAMMINEDICHLOROPLATINUM ON CELL AND TUMOR-GROWTH OF HUMAN HEPATOCELLULAR-CARCINOMA

The inhibitory effects of a combination of Antineoplaston A-10 Injection with a small dose of cis-diamminedichloroplatinum (CDDP) on cell and tumor growth was tested in in vitro and in vivo settings. A human hepatocellular carcinoma cell line (KIM-1) was used for the cell growth and transplanted tumor growth studies. In the cell growth study, one-hour exposure of KIM-1 cells to CDDP in the medium at concentrations of 0.5, 1.0, and 2.0-mu-g/ml inhibited cell growth dose-dependently. Continuous exposure of cultured cells to Antineoplaston A-10 Injection at concentrations of 4, 6, and 8 mg/ml also inhibited tumor growth dose-dependently. The combination of 0.5-mu-g/ml CDDP and 6 mg/ml A-10 Injection inhibited cell growth more than did each agent individually. Electron microscopic study showed well-maintained organelle structures in Antineoplaston A-10 Injection-treated cells compared to CDDP-treated cells. Alpha-Fetoprotein (AFP) production by 10(4) cells in 48 h increased in the A-10 Injection-treated and A-10 Injection + CDDP-treated groups as the concentration of these agents increased. In the tumor growth study, daily administration of Antineoplaston A-10 Injection 75 mg with once a week administration of 20-mu-g of CDDP for 5 weeks inhibited transplanted tumor growth in athymic mice after 33 days of treatment, while administration of 75 mg of A-10 Injection or 20 or 60-mu-g of CDDP alone showed no significant inhibition of tumor growth.