Multi-drug Resistance-associated Gene Ergic-53 And Htnf-¦Á Reversal Of Drug Resistance

Recently, cancer has becoming the second leading cause of mortality in the world. Multidrug resistance(MDR) is a major obstacle of cancer chemotherapy and has been closely associated with chemotherapy failure, over 90% of cancer deaths were related to MDR. So it has becoming a hot topic to understand and overcome drug resistance.The studies on the MDR have been focused on the mechanisms that are caused by adenosine triphosphate-binding cassette(ABC) superfamily: P-glycoprotein (P-gp), Muiltdrug- resistance related protein(MRP) and Breast cancer resistance protein (BCRP) in the ABC superfamily have been proved to play an important roles in the Muiltdrug-resistance in the tumor cell lines. The results of all the studies suggest that the multidrug resistance be caused by multiple factors.There are two sections in this thesis. The first section is about identification of drug resistance-related genes with cDNA microarray and investigation of ERGIC-53(one of the upregulated genes) in MDR tumor cell lines and samples with hematology patiens, and studies on the role of ERGIC-53 in MDR with RNAi etc. That will provide potential new target for diagnosis and therapy of the drug resistant tumor. The second section of the thesis, hTNF-a has been cloned and expressed in E.coli, and then its effect on multidrug resistant tumor cells has been studied.1. Studies on the multidrug resistant related genes.The cDNA microarray which contains 1,176 genes was used to examine relative gene expression between K562/A02 and K562. 12 differentially expressed genes were found, 7 were downregulated and 5 upregulated.Among the upregulated genes, ERGIC-53 is a marker of the ER-Golgi intermediate compartment, which is the mannose-specific non-glycosylated type I membrane protein. The expression of ERGIC-53 in MDR and non-MDR tumor cell...