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Aim: To investigate the anti-tumor effects and mechanisms of interstitial chemotherapy using intra-tumor injection of thermosensitive gel-coated ricin in nude mice bearing a human hepatoma. Methods: In a subcutaneous mouse model of hepatoma, saline, blank gel, ricin, or thermosensitive gel-coated ricin (TGR) was injected directly into tumors. Fourteen days later, eight mice in each group were sacrificed. The tumors were removed and weighed for calculating tumor growth inhibition rate. Serum alpha-fetoprotein levels, as well as hepatic and renal functions, were measured. Tumor tissue was analyzed under an optical microscope. Terminal deoxynucleotidyl transferase mediated dUTP nick end labeling was used to detect the apoptotic index. Moreover, caspase-3 activity and protein expression in tumor tissue were examined. The survival time of the tumor bearing mice was determined. Results: Following interstitial chemotherapy by intra-tumor injection of TGR in nude mice, serum alpha-fetoprotein levels were significantly reduced with no significant impact on hepatic or renal functions. The rate of tumor growth inhibition was 58.5% following a single, local injection. Histological analysis revealed abundant necrosis. The apoptotic index was 45.96 ± 7.41%. Caspase-3 activity was increased, and caspase-3 protein was significantly activated in tumor cells. Compared to the saline group, the survival time of mice in the TGR group was significantly extended. At the observation terminal time, day 120, two mice were still alive and fully recovered. Conclusion: Interstitial chemotherapy by intra-tumor injection of TGR was highly efficient and safe for the treatment of nude mice bearing a human hepatoma. Interstitial chemotherapy exhibits inhibitory effects by inducing apoptosis and directly killing tumor cells. [ABSTRACT FROM AUTHOR]