Relationship Between MDR1, The Types Of Cyclins Expression And TNM Stages In Gastrointestinal Cancers

Objective We have studied the expression of MDR1(Multi-drug Resistance Gene 1) encoded P-gp(P-glycoprotein) in gastrointestinal normal and cancer tissues. At the same time, the primary four Cyclins'expression rules were analyzed in order to classify cancers. At last, we investigated the relationship between the expression level of Mdr1, Cyclin expression type and TNM stage in the gastrointestinal cancers. The aim is to connect MDR1 as the important molecular basis of cancers'drug resistance with cancer cell cycle.Methods We analyzed the P-gp expression level and cell cycle schedule in 27 normal (certified by pathology) gastrointestinal tissue samples from the incisal edge of cancer radical operation by DNA/FITC two-parameter flow cytometry. Besides, the 62 fresh samples from the gastrointestinal cancer operation patients were harvested, then Cyclin (D1, E, A, B) and P-gp were detected by flow cytometry. Equally, the cell cycle schedule of P-gp was analyzed in these cancer tissues. Eventually, pathology reports after the operation were registered for TNM stages.Results P-gp is presenting unscheduled expression in both normal and cancer tissues. Moreover, the disparity of the expression level of P-gp between the normal and cancer tissues in gastrointestinal tract is distinguished through statistical analysis, the expression level in cancer tissues is higher(Wilcoxon test,P<0.05). According to the expression of four Cyclins, four cell cycle types could be divided in the gastrointestinal cancers. These four cell cycle types have correlation with TNM stages(concordance test, Kappa=0.5993,P<0.01) and the expression level of P-gp(Spearman test,rs=0.495,P=<0.01).Conclusion MDR1 expression level in gastrointestinal cancer is higher than normal tissues, and is presenting unscheduled expression. Therefore, the function of drug pump mediated by P-gp has no cell cycle specificity. In the process of gastrointestinal tissue developing from the normal to cancer, the function and expression of P-gp which is a membrane protein originally acting as barrier and ion channel has altered. Four cell cycle types based on the expression of primary four Cyclins have the same significance with TNM stages. The expression of MDR1 is involved in the cell cycle types, prompting that it is related with cancer's TNM stages.