ABSTRACT
Objective To study the mechanisms of the drug resistance of DNA mismatch repair (MMR) deficient color-ectal cancer (CRC) HCT-116 to 5-fluorouracil (5-Fu) .Methods MLH1 deficiency HCT-116 cells were transfected with pcD-NA3 .1-MLH1 Vector .The expression of MLH1 was detected by Western blot .The change of resistance against 5-Fu was ex-amined by detecting the cell viability with CCK-8 kits .The expression of CD133 (cancer stem cell marker ) and CK8 & CK20 (cell differentiation marker) were detected by flow cytometry .Results Comparing to HCT-116 control group ,the viability of HCT-116 cells was markedly decreased (P<0 .01) after stable expressing MLH1 ,accompanied by the down-regulated expres-sion of CD133 on the cell surface .Moreover ,the up-regulation of cell differentiation marker CK8 and CK20 was observed in HCT-116 cells with stable expressing MLH1 .Conclusion Our data indicated that the expression of MLH1 was associated with down-regulated CD133+ stem-like cells in colorectal cancer HCT-116 with MLH1 deficiency .Therefore ,CD133+ stem-like cells may related to the drug resistance of MMR deficiency tumor .This study provides a possible theory to explain the 5-FU resist-ance in the colorectal cancer patients with MMR deficiency .
ABSTRACT
Orphan nuclear receptor NR4A1 from the NR4A subfamily is one of the transcriptional factors that have not identified specific ligands .Previous studies have found that NR4A1 could regulate cell proliferation ,apoptosis ,differentiation and stress responses by changing gene expression ,post-translational modification and interactions between coregulatory pro-teins .Recently ,it has shown that NR4A1 has an abnormal expression in human atherosclerotic lesions and has been identified as a key regulator gene in vascular cells dysfunction .Regulating NR4A1 expression can have an important impact on the prolif-eration of smooth muscle cell and endothelial cell activation ,meanwhile it could reduce inflammation ,foam cell formation and lipid deposition ,inhibit vascular remodeling ,and prevent the development of atherosclerosis .These studies suggest that NR4A1 might be a novel target for drug development in prevention and treatment of atherosclerosis .
ABSTRACT
Sphingosine-1-phosphate receptor 1(S1PR1) is a new member of G protein-coupled receptor family. A great body of data suggest S1PR1 is capable of regulating lots of downstream signaling molecules and cellular processes. It is found that S1P/S1PR1 plays an important role in the development and mainte-nance of pain. However, it is controversial whether activation of S1PR1 would enhance or attenuate pain. Here, recent studies ＜br> and current perspectives are discussed in order to better under-stand the biological and pathological roles of S1PR1 in pain mod-ulation.