The Effect Of High Glucose And Insulin To The Expression And Function Of P-glycoprotein Of MCF-7/ADR Cells

Purpose:Detect the content of P-glycoprotein of MCF-7/ADR cells, analysis the effects of high glucose and high insulin to the expression and function of P-glycoprotein, and preliminarily investigate the effects of Mdrl to breast cancer patients who have diabetes.Methods:Use different concentration of glucose and insulin to culture MCF-7/ADR cells, use Real-time PCR and Western blot and Rhodamine123uptake to detect P-glycoprotein from gene, protein and protein function level. Use fluorescence microscope to detect whether high glucose concentration can cause cell apoptosis, to exclude the influence of apoptosis. Thus we can provide some theoretical guidance for the chemotherapy of breast cancer patients who have diabetes.Results:(1) The relative expression of Mdrl mRNA changes with glucose concentration, especially when it is under11.1mmol/1, it goes sharply up and then down. Compared with5.6mmol/l glucose group,11.1-27.8mmol/l glucose groups have remarkably different expression of Mdrl mRNA. It also changes with fructose concentration. It gradually goes down under5.6-16.7mmol/l fructose groups, but goes up under22.2、27.8mmol/l fructose groups. And compared with5.6mmol/l fructose group,11.1～27.8mmol/l fructose groups have remarkably different expression of Mdrl mRNA. The relative expression of Mdrl mRNA changes with insulin concentration, it goes gradually down with the increase of insulin concentration, compared with0.005-0.01μmol/1insulin groups, the group without insulin has remarkably high expression of Mdrl mRNA.(2) The content of P-glycoprotein changes with the increase of glucose concentration, it has high expression under11.1mmol/1glucose group, and has low expression in16.7-27.8mmol/l glucose group. Compared with5.6mmol/l glucose group, 11.1-27.8mmol/l glucose groups have remarkably different expression of P-glycoprotein (P<0.001). The relative expression of P-glycoprotein changes with insulin concentration, it goes gradually down with the increase of insulin concentration, compared with0.005-0.01μmol/l insulin groups, the group without insulin has remarkably high expression of P-glycoprotein (P<0.001).(3) The function of P-glycoprotein goes down with the increase of glucose and insulin concentration, and the changes have statistical differences.Conclusion:High consentration of glucose and insulin can change the expression of P-glycoprotein of MCF-7/ADR cells, and influence the drug resistance of breast cancer patients who have diabetes. But the molecular mechanism still needs further investigation.