siMTA1-Loaded Exosomes Enhanced Chemotherapeutic Effect of Gemcitabine in Luminal-b Type Breast Cancer by Inhibition of EMT/HIF-α and Autophagy Pathways

Advanced breast cancer holds a poor prognosis for chemotherapy and endocrine therapy resistance. Autophagy is one of the main causes of tumor drug-therapy failure, and increasing evidence shows that EMT also is responsible for that. Metastasis-associated protein1 (MTA1) is up regulated in lots of tumors, which leads to tumor progression and drug resistance. However, the role of MTA1 in chemotherapeutic resistance in luminal-b breast cancer is still unclear. In this paper, our research shows that higher expression of MTA1 accompanies with worse prognosis in luminal-b breast cancer. Knockdown of MTA1 enhances the sensitivity of MCF-7 to gemcitabine and weakens the metastasis ability of MCF-7 in vitro and in vivo. Further, we find that knockdown of MTA1 strengthens the gemcitabine-mediated tumor growth inhibition effect in vivo, through reversion of the EMT process and inhibition of the autophagy process. Furthermore, our research builds the siMTA1-loaded exosomes, which increases the gemcitabine-mediated tumor growth inhibition effect in vivo.