1,25-dihydroxyvitamin D3 dissolved in lipiodol produces a sustained antiproliferative effect in the human hepatoblastoma cell line HepG2

The steroid hormone 1, 25-dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] has potent ial to be used as an anti-tumor agent, but its clinical application has bee n restricted by the strong systemic calcemic activity. Regional administrat ion of the drug dissolved in lipiodol, might be a way of selectively delive ring high concentrations of the drug to lipiodol avid tumor cells without c ausing systemic side effects In acute (1 day treatment) and chronic (5 days treatment) experiments, efficacy of the drug dissolved in ethanol (control ) or lipiodol and subsequently diluted in the culture medium was tested in vitro against the hepatoblastoma cell line HepG2. Using [H-3]thymidine inco rporation and cell count, antiproliferative effects of 1,25-(OH)(2)D-3 diss olved in the two different solvents was compared. Microscopic examination o f cells exposed to the lipiodol containing media revealed intra-cellular pr esence of the oil in abundance. Chronic treatment of cells with either form ulation of 1,25-(OH)(2)D-3 resulted in profound inhibition of cell prolifer ation. However, exposure of cells to 1,25-(OH)(2)D-3 in lipiodol was follow ed by significantly greater and lasting inhibition of cell proliferation in both acute and chronic studies. These results indicate that, 1,25-(OH)(2)D -3 dissolved in lipiodol probably acts as a sustained release drug depot fo rmulation, in which case it could have some potential for the regional trea tment of liver tumors.