Experimental Study Of Arsenic Trioxide On Rabbits With Hepatic Vx-2 Carcinoma By Transcatheter Arterial Infusion

Objective To evaluate the anticancer effect and hepatic toxicity of arsenic trioxide(As2O3) on rabbits with hepatic Vx-2 carcinoma by transcatheter arterial infusion(TAI), to investigate the possible mechanism and its clinical signification .Methods Fifty New Zealand rabbits weighing 2-3kg with hepatic Vx-2 carcinoma were randomly divided into five groups two weeks after implantation, then treated with As2O3 (experimental groups),cisplatin or normal saline (control groups ) by TAI for 7 days consecutively .After 2 weeks adding drug , The tumor inhibitory rate was assessed .The morphological changes of the tumor and hepatic tissue were also investigated under light microscope and transmission electron microscope . Bcl-2, bax and VEGF expression were examined by immunohistochemistry .Results The tumor growth inhibitory rate in experimental groups were 50.31%, 59.58%and 69.71% respectively ,the growth of tumor were obviously inhibited compared with the NS group (p <0.05) . The downregulated bcl-2 expression and the upregulated bax expression (all P < 0.001) were detected by immunohistochemistry ,in comparison withcontrol groups . Significantly decreased VEGF expression was also bserved in As2O3 groups vs the controls(p <0.001) . Gene bcl-2 expression was consistent with VEGF expression. Some tumor cells of experimental groups were showed the typically morphological characteristics of apoptosis under transmission electron microscope .It could be observed in experimental groups which was the swelling of capillary endothelial cells , the necrosis of capillary endothelial cells and the microthrombus in tumor tissue . So it approved that the tumor blood perfusion can be reduced by damage its nutrition blood vessel electively. The mitochondrial morphological changes were obviously different in all groups after As2O3 administration (p <0.05),this cued what As2O3 by TAI can damage the mitochondrial of tumor cells selectively .at the same time the hepatic cells of the rabbits were injuried a certain degree,by comparison the NS groups under light microscope (p <0.001) and transmission electron microscope(p <0.05) . Conclusion As2O3 by TAI induces apoptosis of rabbit,s hepatic Vx-2 carcinoma cells and inhibits liver tumor effectively.The toxicity of As2O3 to the liver of the New Zealand rabbit was also investigated by TAI. Those effects related to the doses of As2O3 .Our results justify the strategy may have a prospect of clinical applications in advanced patients of HCC ,in the meanwhile it is necessary to protect hepatic function of those patients .