Research On The Anti-hepatoma Effect Of Artesunate Nano-liposomes And The Mechanisms Of Mitochondria Inducing Apoptosis

Objective:Comparing with artesunate API (Active pharmaceutical ingredient), anti-hepatoma effect of artesunate nano-liposomes in liver cancer, the influence of apoptosis related gene expression. Explore new safe and effective drμg preparation for the clinical treatment of liver cancer.Methods:Preparation of artesunate nano-liposomes, preparation of artesunate nano-liposomes, HepG2cells and Lo-2cells were treated with PBS、artesunate API and artesunate nano-liposomes. Concentrations and the processing time of the anti-hepatoma effects were observed under the different function conditions. Cell proliferation was measured by methylthiazolyl tetrazolium (MTT) assay. The morphological changes of apoptosis were observed by Hoechst33258staining. Artesunate API and artesunate liposomes were given by intraperitoneal injection to liver cancer xenograft models in nude mice, and the anti-hepatoma effect was observed. RT-PCR was used to detect the mRNA expressions of apoptosis related factors Apaf-1、caspase-9caspase-3in cells and tumor tissue. Immunohistochemical method detection caspase-3protein expression.Results:The results indicated that artesunate API and artesunate nano-liposomes could inhibit the proliferation of HepG2cells in a dose and time dependent manner. IC50of artesunate nano-liposomes was15.997μg/ml, and IC50of artesunate API was15.997μg/ml. Lo-2cells were treated with them, IC50of artesunate nano-liposomes was100.226μg/ml, and IC50of artesunate API was105.54μg/ml; The inhibitoy rate of artesunate liposomes on human hepatoma transplanted tumor in nude mice was32.7%, artesunate API was20.5%, respectively. The mRNA expressions of caspase family genes were up-regulated, and artesunate nano-liposomes group higher than artesunate API group. The differences were statistically significant.Conclusions:Artesunate nano-liposomes could inhibit the proliferation and induce apoptosis of human hepatoma cell line HepG2. The expression of caspase would be one of the important apoptotic inducing factor. Artesunate nano-liposomes show stronger anti-cancer effect than that of artesunate API.