The Function And Mechanism Of AGR2 In Drug Resistant Cancer

Anterior Gradient-2(AGR2)attracted much attention since its discovery.At present,the research focused on the role and mechanism of endogenous and secretory AGR2 in various tumors.The structure of AGR2 protein is special,so it is widely located in the cell and the function is complex and diverse.Recent studies have shown that AGR2 interacts with IGF-1,HIF-1 a,p38,etc.to promote the resistance of breast cancer cells to the treatment of chemotherapeutic drugs.However,these studies are relatively simple for the mechanisms;the function and mechanism of AGR2 in other tumor resistance have not been studied.Through our study,we want to explore the role of AGR2 in the pathogenesis of different tumors and to further summarize the general mechanism of AGR2 in tumor resistance.In this study,the effects and mechanisms of AGR2 on breast cance r and hepatocellular carcinoma resistance were studied.The breast ca ncer cell MCF-7 and hepatocellular carcinoma cell BL-7402 and its dru g-resistant cell BL-7402/FU were used as the tool cells.The results of immunofluorescence assay and Western Blot showed that AGR2 was hig hly expressed in MCF-7 and BL-7402/FU cells,but was weak in BL-7402 cell.The differential expression of AGR2 in hepatocellular carcinoma cell BL-7402 and its drug resistant cell BL-7402/FU is a very intere sting phenomenon,suggesting that AGR2 may play a role in the resista nce of hepatocellular carcinoma cells.The MCF-7-AGR2 knockout cell 1 ine and BL-7402-AGR2 overexpressing cell lines were constructed accor ding to the expression of AGR2,the AGR2 in BL-7402/FU cell was kn ocked down by siRNA.In the BL-7402-AGR2 overexpressing cell line,th e anti-apoptotic ability of the cell was significantly enhanced.The results showed that there were significant differences between the co ntrol cell and the overexpression cell(p=0.00i1<0.01,p=0.0005<0.001).In the MCF-7-AGR2 knockout cell line,the number of apoptotic cell i n the knockout group was increased,that is,the anti-apoptotic abili ty of the cell was decreased(p=0.0003<0.001),and the MTT assay sho wed that the proliferation ability of the knockout cell was also weak ened.In addition,knock down AGR2 in BL-7402/FU cell by siRNA,doubl e staining cells with Annexin V-FITC/PI,then detected by flow cytome try.The result showed that after knock down AGR2,the proportion of apoptosis increased,MTT results showed cell proliferation is also we akened.Based on these results,AGR2 can mediate cell proliferation and apoptosis,so that cells can survive in the efficacy of chemotherapy drugs,then the cells produce drug tolerance,ultimately lead to tumor resistance.In addition,we have a preliminary discussion on the signal pathways that AGR2 relies on in these functions,which lays a foundation for further study of AGR2' s function and mechanism in drug resistant tumor,which may be strategies for drug resistance in tumor.