| Objective: The adriamycin-resistant human breast cancer cell line MCF-7/ADR were used as the experiment subject to investigate the FOLR1 receptor gene and it's downstream gene dihydrofolate reductase gene expression correlated with the breast cancer cell multidrug-resistance.Methods: MTT assay were used to investigate the cytotoxicity of ADR and reversal effect of trimethoprim on MCF-7/ADR cells, real time PCR were used to detect transcriptional levels of folate receptor mRNA and dihydrofolate reductase mRNA of MCF-7/S cells and MCF-7/ADR cells,The protein level of P-gp and FOLRa were detected with Immunocytochemistry.Results: FOLRa receptor mRNA transcriptional levels of MCF-7 cells was higher than MCF-7/ADR cells, dihydrofolate reductase mRNA transcriptional levels of MCF-7/ADR cells was increased; It showed that the The protein level of P-gp of MCF-7/ADR cells was higher than it's of MCF-7/S cells, and The protein level of FOLRa of MCF-7/ADR cells was less than it's of MCF-7/S cells, The concentrations of Trimethoprim of 240μmol·L-1 and under it showed mild inhibitory effect on MCF-7/ADR cells (inhibition rate <20%), while non- reversal effect.Conclusion: The FOLRa receptor transcription level in MCF-7/ ADR cells down-regulated, the transcription level of dihydrofolate reductase in MCF-7/ADR cells up-regulated, the expression of P-gp in MCF-7/ADR cells increased. Those showed the multidrug resistance in MCF-7/ADR cells associated with P-gp increased by The FOLRa receptor transcription level down-regulated and the transcription level of dihydrofolate reductase up- regulated; Trimethoprim had non-reversal effect of multidrug resistance on MCF-7/ADR cells. |
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