Overexpression of miR-134 enhanced the sensitivity of breast cancer cells to doxorubicin by downregulating ABCC1 expression
1
Comprehensive Cancer Center, Sichuan University, Chengdu, Sichuan, China
2
Department of Breast Surgery, West China School of Medicine/West China Hospital of Sichuan University, Chengdu, Sichuan, China
3
Department of Pharmacy, Luzhou People's Hospital, Luzhou, Sichuan, China
Abstract
OBJECTIVE: To detect miR-134 and ABCC1 expressions in doxorubicin-resistant breast cancer cell line and their relationship. STUDY DESIGN: The expressions of miR-134 in doxorubicin-resistant breast cancer MCF-7/ADR cells and nonresistant MCF-7 cells were measured by qRTPCR. ABCC1 mRNA and protein expressions were detected by qRT-PCR and western blot, respectively. The proliferation of MCF-7/ADR cells overexpressing miR-134 was detected by MTT assay after treatment with doxorubicin at IC50. Flow cytometry was used to detect the apoptosis of MCF-7/ADR cells overexpressing miR-134. RESULTS: The miR-134 expression in MCF-7/ADR cells was significantly lower than that of MCF-7 cells (p<0.01). The mRNA and protein levels of ABCC1 in MCF-7/ADR cells were significantly higher (p<0.001). After overexpression of miR-134, only ABCC1 protein expression in MCF-7/ADR cells decreased significantly (p<0.001). IC50 of MCF-7/ADR cells overexpressing miR-134 was 226 ng/mL. The proliferation of MCF-7/ ADR cells overexpressing miR-134 with 226 ng/mL doxorubicin was significantly weaker than that of control group at 48 hours (p<0.05). MCF-7/ADR cells overexpressing miR-134 were significantly more prone to apoptosis than those of the control group after treatment with 226 ng/mL doxorubicin (p<0.01). CONCLUSION: Overexpression of miR-134 in MCF-7/ ADR cells facilitated doxorubicin-induced proliferation inhibitory and proapoptotic effects by downregulating ABCC1 expression, thereby augmenting cell sensitivity to doxorubicin. © Science Printers and Publishers, Inc.