Comparison of Anti-hepatocarcinoma Effect of Curcumin and Hydrazincurcumin and Mechanism Study / 中国药房

ABSTRACT

OBJECTIVE：To compare the an ti-hepatocarcinoma effects of curcumin （CUR）and its derivative hydrazincurcumin （HZC），and to explore the mechanism. METHODS ：MTT assay was used to detect the effects of CUR or HZC （2.5，5，10，20， 40，80 μmol/L）on the proliferation of HepG 2 cells. Flow cytometry was used to detect the effects of CUR or HZC （10，20，40 μmol/L）on cell cycle distribution and apoptosis of HepG 2 cells. Western blotting assay was used to detect the effects of CUR or HZC（10，20，40 μmol/L）on the expression of apoptosis-related protein in HepG 2 cells. The male SD rats were randomly divided into normal control group （n＝10），CUR control group （n＝10），HZC control group （n＝10），model group （n＝30），CUR protection group （n＝30）and HZC protection group （n＝30）. CUR control group and HZC control group were given CUR 85917439。E-mail：zhaoji-an-88@163.com or HZC （80 mg/kg） intraperitoneally. Model group ，CUR protection group and HZC protection group were given diethylnitrosamine （50 mg/kg）intraperitoneally to establish hepatocarcinoma model ；at the same time ，2 protection groups were given CUR or HZC （80 mg/kg）intraperitoneally，twice a day，for consecutive 12 weeks. During medication ，the change of body weight and death of rats were recorded. Twenty four weeks later，liver index of rats was calculated and appearance was observed ；the number of cancer nodules was counted ；HE staining was used to observe the pathological changes of liver tissue and calculate the nuclear division index of hepatocarcinoma ；the proliferating cell nuclear antigen （PCNA）index was detected by immunohistochemistry. RESULTS ：CUR and HZC could increase the inhibitory rate of HepG 2 cells（P＜0.05），and increased the percentage at G 0/G1 phase and apoptotic rate of HepG 2 cells（P＜ 0.05）. CUR and HZC could significantly decrease the protein expression of p-JAK 2，p-STAT3，Bcl-2 and Bcl-xl ，while increased the protein expression of Bax ，Cyt-c，Caspase-9，Caspase-3 and PAPR （P＜0.05）. Above effects of HZC were significantly better than those of CUR （P＜0.05）. The results of animal experiment showed that there was no death ，no liver canceration and no pathological changes in liver appearance and tissue section of the three control groups ；there was no statistical significance in body weight and its increased weight ，liver index ，nuclear division index of carcinoma or PCNA index （P＞0.05）. Compared with model group， survival rate of rats were increased significantly in CUR protection group and HZC protection group ， while hepatocarcinoma incidence and the number of cancer nodules were decreased significantly （P＜0.05）；body weight and its increased weight were increased significantly ，while liver index ，nuclear division index of carcinoma and PCNA index were decreased significantly （P＜0.05）. There were some pathological changes in liver appearance and tissue section ；cancerous lesions with focal necrosis or cancerous lesions with patchy necrosis were observed. There was no statistical significance in the improvement of above indexes in 2 protection groups （P＞0.05）. CONCLUSIONS ：HZC could inhibit the proliferation and induce apoptosis of HepG 2 cells by inhibiting JAK 2/STAT3 signaling pathway and regulating the activation of mitochondrial endogenous pathway，which shows stronger anti-hepatocarcinoma effect in vitro than CUR. On the other hand ，there was no significant difference in the improvement of liver caner indexes in hepatic cancer model rats between HZC and CUR.