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Objective: To investigate the effect of microrna-221/222 (miR-221/222) on DOX resistance of breast cancer MDA-MB-231/doxorubicin (DOX) cells. Methods: miR-221/222 inhibitor (miR-221/222 inhibitor) was transfected into MDA-MB-231/DOX cells by liposome method, the blank control group and the negative control group were set up meanwhile. The transfection efficiency and expression level of miR-221/222 in MDA-MB-231 cell line and cell line MDA-MB-231/DOX cell line was detected by real time fluorescent quantitative PCR (qRT-PCR); the change of drug sensitivity of MDA-MB-231/DOX cells to dox after 48 hours of transfection was detected by CCK-8 tests; the apoptosis rate of MDA-MB-231/DOX cells was detected by flow cytometry (FCM); the upregulation of pro-apoptotic protein p53 up regulates apoptosis (PUMA), bcl-2 protein modifying factor (BMF) and cyclin kinase inhibitor p27 (p27kip1) in MDA-MB-231/DOX cells were detected by Western blotting (WB).Results: The expression level of miR-221/222 in MDA-MB-231/DOX cells was higher than that in MDA-MB-231 cells (P<0.05), the expression level of miR-221/222 in miR-221/222 inhibitor transfected by MDA-MB-231/DOX cells was lower than that in the blank control group and the negative control group (P<0.05) after 96 hours of treatment; compared with the blank control group, the expression level of miR-221/222 inhibitor transfected by MDA-MB-231/DOX cells was lower than that in the blank control group (P<0.05). The apoptotic rate of the cells increased significantly and the expression of apoptosis promoting protein puma, BMF and p27kip1 in the cells increased (P<0.05); the 50% inhibitory concentration (IC50) of drug resistance cells in the inhibitor group was significantly lower than that in the blank control group and the negative control group (P<0.05). Conclusion: miR-221/222 can increase the resistance of MDA-MB-231/DOX cells to DOX, [ABSTRACT FROM AUTHOR]