ASAC Inhibited Onto H22 Hepatoma Bearing Mice In Vivo And Inducement Differented To H22 Or HL-60 Cell Lines

Sachs has put forward the concept of differentiation therapy for the first time in 1970's. Chinese researchers succeeded in acute promyelocytic leukemia therapy through induced differentiation with all-trans-retinoic acid (ATRA) for the first time in the middle of 1980's, and improved survival quality of patients significantly. There has been an increasing interest in compounds that inhibit the proliferation of cancer cells and induce malignant cells to differentiate into normal cells, and these compounds are expected to be a new type of anticancer agent. It's already proved that the effect of anti-tumor of ASAC was stronger than other arsenic agents. Although the ability of apoptosis of ASAC is better than that of As2O3 in vitro, it is also faint to tumor. In order to know much more about anti-tumor mechanism of ASAC, the author evaluated not only the toxicity of ASAC on mice but also the effect of inducing differentiation cells in vitro. In this study, LD50 of ASAC is determined by the research of acute toxicity experiment with i.v and i.g respectively. The acute toxicity results can be observed through the experimental H22 hepatoma bearing mice, and the impact on viscera or tumor tissue can be determined from pathologic tissues. HL-60 cell are cultured in vitro and the ASAC is added into the culture system. The cell proliferation, morphology, the NBT reduction and phagocytosis of the cells are observed. The effects of differentiation on experimental H22 hepatoma cell then are obtained. The results show that LD50 are 727.78mg/kg and 1342.76mg/kg by i.v and i.g respectively in vivo, and their toxicity are far from lower than As2O3. The ratios of inhibition in the two different forms administration, i.v and i.g, are obviously high on experimental H22 hepatoma bearing mice, and the former is better than the latter. Assayed pathology shows ASAC makes cancer cells dramatically decreased, but the viscera are not obviously damaged. In vitro the results show that the proliferation of HL-60 cells and H22 cells are inhibited by ASAC, which is higher than that of the control group (P<0.01). At the dose of 10-6 mol/L, ASAC makes ALP energy, phagocytosis ability and NBT reaction of HL-60 cells and H22 cells increased. In a word, the toxicity of ASAC is lower than that of As2O3, moreover ASAC is more effective on anti-tumor. ASAC can obviously improve the differentiation of HL-60 cells and H22 cells but shows lower toxicity, increasing dose may be attempted.