Everolimus inhibits breast cancer cell growth through PI3K/AKT/mTOR signaling pathway

Abstract

Breast cancer is one of the most prevalent malignancies and the leading cause of cancer-associated mortality in women worldwide and in China. Everolimus (C53H83NO14) is an efficient anti-cancer drug for breast cancer which targets mammalian target of rapamycin (mTOR). The present study investigated the inhibitory effects of everolimus on breast cancer cells and an MCF-7-bearing mouse model. The potential mechanism of the everolimus-mediated decrease in growth and aggressiveness of breast cancer cells was reported. Results demonstrated that everolimus significantly inhibited breast cancer cell growth, migration and invasion. It was demonstrated that everolimus induced apoptosis through decreasing B cell lymphoma (Bcl)-2 and Bcl-w and increasing caspase-3 and caspase-8 expression levels in breast cancer cells. It was observed that everolimus decreased phosphoinositide 3-kinase (PI3K), protein kinase B (AKT) and mTOR expression levels in breast cancer cells. Results additionally demonstrated that PI3 K overexpression prevented that everolimus-mediated inhibition of growth and aggressiveness in MCF-7 cells. In vivo assays demonstrated that everolimus treatment markedly inhibited tumor growth in the MCF-7 bearing mouse model. Overall, these data indicate that everolimus inhibits growth and aggressiveness of breast cancer cells through the PI3K/AKT/mTOR signaling pathways, suggesting the PI3K/AKT/mTOR signaling pathway may act as a therapeutic target for the treatment of human cancer.