The Effect To Cell Cycle Of Folic Acid And Methylenetetrahydrofolate Reductase Gene Polymorphism To Breast Cancer Cell Line MCF-7/ADR

Objective:To explore the correlation of folic acid, folic acid receptor and the methylenetetrahydrofolate reductase (MTHFR) C677T and A1298C gene polymorphism in breast cancer cell line MCF-7/ADR.Methods:After interfered with different concentrations of folic acid, FCM detected the cycle distribution situation of the cell line MCF-7and cell line MCF-7/ADR; RT-PCR detected the transcription levels of two cell’s FOLR-1, mdr-1mRNA; used PCR-RFLP method to detect the genotype polymorphism of expression of MTHFR C677T and A1298C in cell line MCF-7and cell line MCF-7/ADR.Results:Compared folic acid concentration of270nmol/L or more group with90nmol/L or less group in MCF-7cells, the percentage of cells in G0/G1phase increased, it showed statistical differences(P<0.05), it was the same in MCF-7/ADR cells. In MCF-7cells, compared folic acid concentration of270nmol/L or more group with90nmol/L or less group, the percentage of cells in S phase decreased, the difference showed significant(P<0.05); In MCF-7/ADR cells, each folic acid concentration group of30nmol/L、90nmol/L、270nmol/L、810nmol/L、2430nmol/L compared with0nmol/L group, the percentage of cells in S phase decreased, the change was in a dose-dependent manner, the difference showed significant(P<0.001). FOLR level of gene transcription in MCF-7cells was higher when compared with MCF-7/ADR cells, but mdr-1gene transcription level in MCF-7cells was lower compared with MCF-7/ADR cells; MTHFR gene C677T and A1298C transcriptional level had no difference between MCF-7cells and MCF-7/ADR cells; MCF-7had MTHFR A1298C and C677T gene polymorphism after the action of restriction enzyme, however MCF-7/ADR cells only exist MTHFR C677T gene polymorphism.Conclusion:1. The inhibitory action for DNA synthesis phase was more remarkable in the MCF-7/ADR cells.2. The low express of folic acid receptor in MCF-7/ADR cells may have relationship with the primary or secondary drug resistant.3. In MCF-7/ADR cells, the disappearance of genotype polymorphism of A1298C in MTHFR may have relationship with the increased transcription of mdr-1.