Mechanism Of Sirtuin Mediated Chemoresistance In Hepatocellular Carcinoma

PART â…  Experimental Study on SIRT1modulate key genes such as ATG7/XIAP and its mechanism of chemoresistance in hepatocellular carcinomaThe most common reason of tumor treatment failure is chemoresistance. Hepatocellular carcinoma is not sensitive to chemotherapy. Many traditional chemotherapy drugs like Fliorouracil, Mitomycin, Epirubicin, Cisplatin were used to treat hepatocellular carcinoma.But they got very low efficiency for single use. There are no standard treatment for the chemotherapy of hepatocellular carcinoma up to now.Sirtuin is closely related to chemoresistance and multidrug resistance.SIRT1is the key gene which modulated autophagy and apoptosis. So sirtuins might be the potential targets for the therapy of tumors. Three genes and two cell lines were used to find out if SIRT1can modulate key genes such as ATG7/XIAP and its mechanism of chemoresistance in hepatocellular carcinoma.AIM To investigate if SIRT1can modulate ATG7/XIAP and its mechanism of chemoresistance in hepatocellular carcinoma.METHODS HepG2and HCC-LM3cells were both incubated with Fliorouracil at different concentrations, Fliorouracil was act for HCC-LM3combined with sirtl-siRNA/3MA/Embelin.We used resveratrol and ex527to regulate SIRT1expression.The proliferation of hepG2and HCC-LM3cells was assessed by MTT assay, the mRNA expression of SIRT1, ATG7, XIAP were detected by real time PCR.RESULTS HCC-LM3showed drug resistance with Fliorouracil. The expression level of SIRT1, ATG7, XIAP in HCC-LM3are higher than hepG2. Fliorouracil combined with SIRT1-siRNA,3MA,Embelin can significantly inhibited the proliferative response of cancer cells. SIRT1can positively regulates key genes such as ATG7and XIAP.CONCLUSION The expression level of SIRT1, ATG7, XIAP in drug resistant hepatocellular carcinoma cells are high. Knocking down the expression of SIRT1, ATG7, XIAP in HCC-LM3can sensitize chemoresistance. The drug-resistant mechanism can be due to that SIRT1may positively regulates ATG7and XIAP PART â…¡Study of Expression and correlation of SIRT1, ATG7and XIAP in hepatocellular carcinoma tissuesAIM To study the correlation among SIRT1, ATG7, XIAP and their clinical relevance in hepatocellular carcinoma tissues.METHODS The mRNA expression of SIRT1, ATG7, XIAP were detected by real time PCR. Analysis of the relation were performed using statistical SPSS among three genes and the degree of tumor differentiation, Child-Pugh, AFP, pathological grades and so on. RESULTS The expression level of SIRT1, ATG7, XIAP in hepatocellular carcinoma are significantly higher than normal liver tissue. A significant positive correlation was found among SIRT1, ATG7, XIAP.But the expression level of three genes have nothing to do with the degree of tumor differentiation, pathological grades, Child-Pugh, AFP.CONCLUSION The expression of Sirtuin,autophagy and apoptosis in hepatocellular carcinoma are higher than normal liver tissue. The correlation analysis indicated that sirtuin has a positive correlation with autophagy and apoptosis,But the expression level of them are not relevant to the degree of tumor differentiation, pathological grades, Child-Pugh, AFP.