| Purpose:There are still some difficulties we faced in the clinical treatment of HCC. The implantation metastasis in liver cancer operation is an urgent problem needed to be solved. In this study, we have investigated the effects of individual and joint action of organic silicone quaternary ammonium salt (Jieyoushen) and5-fluorouracil (5-FU) in human hepatocellular carcinoma SMMC7721cells lines and R15cell lines of rat in vitro. Here we assessed the characteristics of the drugs to explore the effects of individual and joint action of Jieyoushen and5-FU.Methods:MTT assay was used to investigate the inhibitory effects of these agents. Electron microscopy and Hoechst33342staining were used to observe the morphological changes of liver cell lines treated with Jieyoushen and5-FU. Flow cytometry were performed to detect the cycle and apoptosis of liver cell lines with Jieyoushen and5-FU. The expression of caspases-3and8, bax, bcl-2, and survivin protein in these cells were determined by western blotting.Results:The results of MTT assays showed that single and joint action Jieyoushen and5-FU inhibited the proliferation of liver carcinoma cell lines in a dose-and time-dependent manner respectively. And electron microscopy and Hoechst33342staining showed that characteristic apoptotic bodies were visible in apoptotic cell treated with Jieyoushen and5-FU. Flow cytometry results indicated that the percentages of cells at G0/G1phase gradually increased, while gradually decreased during S phase after the treatment. The medication leds to the changes on expression of proteins caspases-3,-8, bax, bcl-2and survivin. Compared with the control group, the expression levels of bax, caspase-8and caspase-3protein increased significantly in the SMMC7721and R15cells after24hours treatment, meanwhile, the bcl-2protein expression decreased significantly.Conclusions:It can be concluded that the combination of Jieyoushen with5-FU showed a better inhibitory effect than either agent alone. The mechanism of action could be the synergistic arrest of the cell cycle, induction of apoptosis, activation of caspases-3,8and9, and down-regulation bcl-2expression. So, it can be indicated that the combination of Jieyoushen with5-FU exerted a synergistic anti-cancer effect on HCC growth, via the impact on the proteins of mitochondrial signaling pathway and the positive film, produced by Jieyoushen, which had a mechanical shielding effect on tumor cell membrane. So Jieyoushen will be a useful ancillary drug to improve the effectiveness of chemotherapeutic agents in the treatment of live cancer,which might be useful for the further development of anticancer drugs. |
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