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

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Abstract
The inhibitory effects of a combination of Antineoplaston A‐10 Injection with a small dose of m‐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 μg/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 μg/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. α‐Fetoprotein (AFP) production by 104 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 μg 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 μg of CDDP alone showed no significant inhibition of tumor growth.