TTF1-NP Inhibit The Growth Of Phc In Rats Through Caspase Pathway Of Endoplasmic Reticulum Stress

Objective:Through constructing the rat hepatocellular carcinoma model which was induced by diethylnitrosamine (DEN), hepatocellular carcinoma cells were induced to apoptosis. Explore the inhibitory the growth of hepatocellular carcinoma in rats and inhibition by Caspase pathway in endoplasmic reticulum stress.Method:54 SD rats were used in this experiment and randomly divided into two groups:the control group with 9 rats and the experimental group with 45 rats. The experimental group rats in hepatocellular carcinoma model drink DEN solution free, and the control group rats drink water. At the 20 weeks, the experimental groups were divided to the model group, rats included doxorubicin group, low/middle/high does in TTF1-NP groups, and the adriamycin group. Three rats were chosen from each of the TTF1-NP groups and observed the inhibition mechanism by PET-CT. The experimental groups took the medicine once every 2 days,7 times in total, and then the chosen rats had PET-CT detection again. When the experiment was finished, all the rats were killed after anesthetized, then the livers were tested by HE stain. Western Blot was used to detect the protein expression of GRP78, TRAF2, Caspase-12 and cleaved Caspase-3.Result:1. During process of hepatocellular carcinoma, the weights decreased, hair tarnish, the spirits atrophy and feeding were gradually reduced in experimental rats. The livers were rough, and dark with bleeding.2. The results of PET-CT show that there were tumors in rats’ livers by 18F-FDG tracing. According to the results, after taking medication the tumors of infection groups became smaller. With the dose of TTF1-NP increased, the value of SUV was declined, which had a dose-response relationship.3. Results of HE indicated that the hepatocytes in control group had a normal cell morphology, and in experimental groups were swelling. In the doses of TTF1-NP groups, the hepatocytes became normal.4. The results of Western blot show that comparing with the control group, TRAF2, GRP78, Caspase-12 and cleaved Caspase-3 in the hepatocytes in model group were increased. The proteins of different doses of TTF1-NP groups were expressed increasingly.Conclusion:TTF1-NP inhibited the growth of hepatocellular carcinoma in rats. Caspase pathway is one of the mechanisms that TTF1-NP inhibited hepatocellular carcinoma growthing in rats by endoplasmic reticulum stress.