Objective To observe the effects of soluble epoxide hydrolase inhibitors tAUCB on cholesterol efflux in adipocytes. Methods 3T3-L1 preadipocytes were induced to differentiation and maturation. Cells were stimilated with 100μg/L LPS after starved for 24 hours, then tAUCB in various concentrations(1 ,10,50,100 μmol/L)were added for 24 h, or incubated with the peroxisome proliferator activated receptor gamma (PPARy) antagonist GW9662 (5 μmol/L).0μmol/L tAUCB treated group was taken as empty control. After then, the mRNA expression of PPARγ and adenosine triphosphate binding cassette transporter Al (ABCA1) in cells were determined via realtime-PCR, the amounts of protein expression of PPARγand ABCA1 in cells were detected by Western blot, the efflux rates of 3H-cholesterol in cells were detected by means of liquid scintillation counter. Results tAUCB could dose-dependently increase the apolipoprotein A1 (apoA1)-mediated cholesterol efflux in adipocytes. After stimulated by 1, 10,50,100 μmol/L tAUCB, cholesterol efflux rates were (5.93±0.66) %, (7.40 ± 0. 43) %, (8. 30 ±0. 34)% ,(9.77±0.42)% respectively, there were significant difference after treated by 10-100 μmol/L tAUCB compared with control(5.67±0.17)%(P＜0.05). With the concentration of tAUCB increased,ABCA1, PPAR mRNA and protein expression were also dose-dependently up-regulated. GW9662 could significantly inhibit the effects of tAUCB, and then reduce the cholesterol efflux and the expression of PPARγ and ABCA1 in adipocytes. Conclusions tAUCB could up-regulate PPARγ expression in adipocytes, and promote the cholesterol efflux of adipocytes via apoA1-ABCA1 pathway, which might decrease the cellular cholesterol accumulation in adipocytes.

Background:Platinum?based chemotherapy is the ifrst?line treatment of non?small cell lung cancer (NSCLC); it is therefore important to discover biomarkers that can be used to predict the effcacy and toxicity of this treatment. Four important transporter genes are expressed in the kidney, including organic cation transporter 2 (OCT2), multidrug and toxin extrusion 1 (MATE1), ATP?binding cassette subfamily B member 1 (ABCB1), and ATP?binding cassette subfamily C member 2 (ABCC2), and genetic polymorphisms in these genes may alter the effcacy and adverse effects of platinum drugs. This study aimed to evaluate the association of genetic polymorphisms of these transporters with platinum?based chemotherapy response and toxicity in NSCLC patients. Methods:A total of 403 Chinese NSCLC patients were recruited for this study. All patients were newly diagnosed with NSCLC and received at least two cycles of platinum?based chemotherapy. The tumor response and toxicity were evaluated after two cycles of treatment, and the patients’ genomic DNA was extracted. Seven single?nucleotide polymorphisms in four transporter genes were selected to investigate their associations with platinum?based chemo?therapy toxicity and response. Results:OCT2 rs316019 was associated with hepatotoxicity (P=0.026) and hematological toxicity (P=0.039), and MATE1 rs2289669 was associated with hematological toxicity induced by platinum (P=0.016). In addition,ABCC2 rs717620 was signiifcantly associated with the platinum?based chemotherapy response (P=0.031).ABCB1 polymor?phisms were associated with neither response nor toxicity. Conclusion:OCT2 rs316019,MATE1 rs2289669, andABCC2 rs717620 might be potential clinical markers for predicting chemotherapy toxicity and response induced by platinum?based treatment in NSCLC patients. Trial registration Chinese Clinical Trial Registry ChiCTR?RNC?12002892