Tetrandrine-Induced Autophagy in MDA-MB-231 Triple-Negative Breast Cancer Cell through the Inhibition of PI3K/AKT/mTOR Signaling

The present study examined the effects of tetrandrine suppressing proliferation, targeting LC3, p62, and Beclin-1 autophagy genes by inhibiting PI3K/AKT/mTOR signaling in Triple-negative breast cancer (TNBC) MDA-MB-231 cell. Cell viability and apoptosis were evaluated by MTT and Annexin-V/PI double staining. Cytotoxicity was determined with LDH assay. Western Blot and Immunofluorescence were used to measure the protein levels of p62/SQSTM1, Beclin1, LC3-II/LC3-I, and PTEN/PI3K/AKT/mTOR signaling. Results showed that tetrandrine inhibited the MDA-MB-231 cell proliferation and induced the apoptosis. Tetrandrine at doses of 12.8, 16.1, and 25.7μmol/L showed significant cytotoxicity on MDA-MB-231 cells (p<0.01). Tetrandrine induced MDA-MB-231 cell autophagy by decreasing p62/SQSTM1 expression, improving the expression of Beclin1 and LC3-II/LC3-I (p<0.01), inhibiting the PI3K/AKT /mTOR pathway by downregulating the expression of p-AKT /AKT, p-PI3K/PI3K p110α, and p-mTOR /mTOR and upregulating PTEN expression. These findings revealed that tetrandrine could suppress proliferation and induce autophagy in MDA-MB-231 cell by inhibiting the PI3K/AKT/mTOR pathway and might be a promising anti-triple-negative breast cancer drug.