The MCF-7 cells were induced by concentration gradient increasing method to establish the DDP cell strain MCF-7/DDP.Then miR-138-5p mimics or hypoxia inducible factor-1α（HIF-1α） overexpression plasmid were transfected into the MCF-7/DDP cells separately or simultaneously. The MCF/DDP cells were divided into negative control group（NC group，transfected with miR-138-5p mimics negative control），miR-138-5p mimics group（transfected with mir-138-4p mimics），miR-138-5p mimics+Vector group （transfected with miR-138-5p mimics and empty plasmid）and miR-138-5p mimics+HIF-1α group（tranfected with miR-138-5p mimics and HIF-1α overexpression plasmid）；and the other MCF-7/DDP cells without transfection were used as blank control group.The cells were treated with different concentrations （0， 10， 20， 40， 80 and 100 μmol·L^－1） of DDP for 24 h and the proliferation activity of cells was detected by MTT， and half inhibitory concentration （IC₅₀） and drug resistance index （RI） were calculated. The expression levels of miR-138-5p and HIF-1α mRNA in the cells were detected by Real-time fluorescence quantitative polymerase chain reaction （qRT-PCR）； flow cytometry was used to detect the apoptotic rate of cells； Western blotting method was used to detect the expression levels of HIF-1α，P-gp and MRP1 proteins in the cells. TargetScan software was used to predict the target binding sites of miR-138-5p and HIF-1α， and the dual luciferase reporter system was used to verify the targeting relationship between miR-138-5p and HIF-1α.

The IC₅₀ of drug-resistant cell strain MCF-7/DDP for DDP was significantly higher than that of its parent MCF-7 cells （P<0.01）， and the RI value was 5.72. Compared with parental MCF-7 cells， the miR-138-5p expression level in drug-resistant cell strain MCF-7/DDP was markedly reduced （P<0.01）， while the HIF-1α mRNA and protein expression levels were significantly increased （P<0.01）. Compared with blank control group and NC group， the miR-138-5p expression level and apoptotic rate in miR-138-5p mimics group were significantly increased （P<0.01），while the HIF-1α protein expression level and the proliferation activity of cells were significantly decreased （P<0.01）. Compared with NC group， the luciferase activity of wild-type HIF-1α cells in miR-138-5p mimics group was markedly decreased （P<0.01）. Compared with miR-138-5p mimics+Vector group， the proliferation activity of cells in miR-138-5p mimics+HIF-1α group was significantly increased （P<0.05）， the apoptotic rate of cells was significantly decreased （P<0.01），and the expression levels of HIF-1α， P-gp and MRP1 proteins in the cells were significantly increased （P<0.05）.

miRNA-138-5p inhibits the expression of HIF-1α and down-regulates the expression levels of resistance-related proteins P-gp and MRP1， thereby enhances the sensitivity of MCF-7/DDP cells to DDP.