Drug Resistance Mechanism And Signaling Pathway Of ABCG2 And MDR1 In Breast Cancer

Part I:To explore the expression and biological significance of ABCG2 and MDR1 protein in breast tumor tissues.Objective: To investigate the expression and biological significance of MDR1 and ABCG2 protein in breast tumor tissues.Methods: Through immunohistochemitry, to explore the expression and biological significance of ABCG2 and MDR1 protein in 186 breast tumor casesResults:(1) ABCG2 and MDR1 were mainly expressed in the breast invasive ductal carcinoma cells cytoplasm and membrane.The expression of ABCG2 protein in breast invasive ductal carcinoma was higher than that in benign tumor tissues.The expression of ABCG2 increased gradually with the degree of malignancy(P=0.001,Z=-3.199)with statistical significance. The positive expression of MDR1 in breast invasive ductal carcinoma was higher than that in IDH with statistical significance(P=0.015);(2)In invasive ductal breast carcinoma with lymph node metastasis of MDR1 positive expression rate was high and the difference was closely to the statistical significance(P=0.059).Conclusion: ABCG2, MDR1 protein was related to the degree of malignancy of breast tumors. Part II:To study the regulation mechanism of ABCG2 and MDR1 in breast cancer cell line and its signal pathway.Objective: To study the regulation mechanism of ABCG2 and MDR1 in breast cancer cell lines and its signal pathway by using doxorubicin-sensitive breast cancer cells--MCF-7 and doxorubicin-resistant breast cancer cells--MCF-7 ADR after DOX treament.Methods: We detected the uptake of DOX in MCF-7 and MCF-7 ADR cells by Flow Cytometry and intracellular DOX accumulation detecting by Fluorescence Spectrophotometer. To study the regulation mechanism and MAPK/ERK,PI3K/AKT signal pathway of ABCG2 and MDR1 in breast cancer cells by Western blot.Results:.(1) Compared with MCF-7, the fluorescence intensity of DOX and intracellular DOX accumulation in MCF-7 ADR decreased obviously.(2) DOX treatment and signal pathway blocking experiments results show that after DOX treatment ABCG2 and MDR1 protein expression was significantly up-regulated in MCF-7 ADR cells,and with ERK and AKT pathway blocking, they were down-regulated.And ABCG2 protein expression in MCF-7 cells was only up-regulated and was down-regulated with ERK signal pathway blocking. Blocking the ERK and AKT signaling pathway can be different degreet increase the uptake of DOX in MCF-7 ADR cells and increase the inhibition of MCF-7 ADR cells; While AKT signal pathway blocking can significantly improve the inhibition of MCF-7 ADR cells, and the difference has statistical significance(P <0.001).Concusions: ABCG2 and MDR1 protein has closely related with DOX resistance mechanism. Blocking ERK and AKT signal pathway can reduce the expression of ABCG2, MDR1 protein, and enhance the effect of DOX treatment.