Regulation of cell growth of hepatoma cells by differentiation inducers and basic investigations for its clinical application

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The possibility of induction of cellular differentiation in human hepatoma cells were investigated. Among the agents investigated, sodium butyrate (SB) is the most possible agent to differentiate human hepatoma cell lines, HCC-T and HCC M.The cell growth, anchorage-dependency and transplantability into a nude mouse of HCC-T and HCC-M were significantly inhibited by SB treatment. The RNA expression of albumin was increased, that of alphafetoprotein was decreased and that of myc was decreased by SB.Some antigen expressions on these cells were changed by SB.The liver-specific antigen which is detected by a mouse monoclonal antibody (H2) was significantly increased by SB treatment. The expression of laminin and fibronectin was significantly decreased and lymphokine-activated killer(LAK)sensitivity was decreased according to the decrease of laminin expression. The decrease of LAK sensitivity was abrogated by anti-laminin. The changes of calcium influx and DNA could not be detected by available instruments. SB did not decrease mitochondrial function and did not induce apoptosis in HCC-T and HCC-M.The in vivo administration of SB (50 mg X 3/nude mouse/w) did not decrease tumor size of transplanted HCC-M cells, although some histological shange was suggested. These results indicate that solid tumors such as hepatoma could be differentiated by SB.SB-treated hepatoma cells functionally came near to hepatocytes and some antigenic shange was induced.