Nano-curcumin attenuates tamoxifen resistance and malignant progression in ER-positive breast cancer cells by inhibiting the PI3K/AKT/mTOR signaling pathway

Breast Cancer (BC) is one of the most prevalent malignant tumors among women, with Estrogen receptor (ER)-positive patients constituting approximately 70 % of all cases. Endocrine therapy is currently a treatment option for patients with ER-positive BC; however, the development of resistance significantly limits the effectiveness of this treatment. Nano-curcumin (Nano-CUR) possesses Anticancer properties and enhances bioavailability by improving the hydrophobic character of curcumin (CUR). However, the underlying mechanism by which Nano-CUR affects tamoxifen (TAM) resistance in ER-positive BC remains unknown. Here, we found that Nano-CUR promoted Apoptosis and cell cycle arrest, inhibited cell proliferation and reduced the levels of Cancer Stem Cells (CSCs)-related markers, including octamer-binding protein (OCT4), Nanog homeobox (NANOG) and sex-determining region Y-box 2 (SOX2) in TAM-resistant BC cells. Additionally, Nano-CUR demonstrated the ability to inhibit tumor malignant progression in TAM-treated BC mice. Mechanistically, Nano-CUR blocked the activation of the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) pathway in MCF-7/TAM and T47D/TAM cells. The activation of this pathway by its activators (PI3K Activator 740Y-P, Akt Activator SC-79, and mTOR Activator MHY1485) effectively alleviated the anti-tumor effect induced by Nano-CUR in TAM-resistant BC cells. Collectively, these findings reveal that Nano-CUR contributes to the reduction of tumorigenesis and TAM resistance in ER-positive BC cells by inhibiting the PI3K/Akt/mTOR signaling pathway.

ER-positive breast cancer; Nano-curcumin; PI3K/AKT/mTOR pathway; Tamoxifen resistance.