Ailanthone exerts anticancer effect by up-regulating miR-148a expression in MDA-MB-231 breast cancer cells and inhibiting proliferation, migration and invasion.

Breast cancer is one of the most common malignant tumors in women with high mortality. Recent evidences have demonstrated that Ailanthone (AIL) could effectively inhibit tumor growth. However, whether AIL exerts anti-tumor effect on breast cancer remains unclear. The study aimed to investigate the effect of AIL on cell proliferation, apoptosis, migration and invasion in MDA-MB-231 cells.After treatment with different concentrations (0-25 μM) of AIL, cell viability was detected by CCK-8 assay, and 10 μM AIL was noted as the optimum concentration for the following experiments. Then, cell proliferation, apoptosis, migration, invasion and relative protein levels were examined by BrdU, flow cytometry, Transwell assays, and western blot, respectively. The expression vectors of miR-148a mimic, miR-148a inhibitor were transfected into MDA-MB-231 cells, and the above experiments were determined again. The signal pathways of AMPK and Wnt/β-catenin were finally analyzed by western blot assay.Cell viability was significantly decreased by AIL in a dose-dependent way. Moreover, AIL reduced the proliferation rate, and modulated CyclinD1, p53 and p21 expressions. AIL remarkably induced cell apoptosis with an increase in cleaved-Caspase-3/-9 expressions. Further, cell migration and invasion were decreased after treatment of AIL in MDA-MB-231 cells. AIL significantly up-regulated miR-148a expression. The effect of AIL on MDA-MB-231 cells was significantly enhanced by miR-148a overexpression, but reversed by miR-148a inhibition. Besides, we found that AIL blocked AMPK and Wnt/β-catenin signal pathways by regulating miR-148a.These data demonstrated that AIL inhibited proliferation, migration and invasion of MDA-MB-231 cells by regulating miR-148a.