BAMBI overexpression together with β-sitosterol ameliorates NSCLC via inhibiting autophagy and inactivating TGF-β/Smad2/3 pathway

• DOI: 10.3892/or.2017.5508
• Publication Date: 2017-03-15T04:41:36Z
• Authors: Xingchun Wang; Minjie Li; Mengyao Hu; Ping Wei; Wei Zhu
• Keywords: 0301 basic medicine; Lung Neoplasms; Genetic Vectors; Membrane Proteins; Smad2 Protein; Sitosterols; Up-Regulation; 3. Good health; Gene Expression Regulation, Neoplastic; Mice; 03 medical and health sciences; A549 Cells; Transforming Growth Factor beta; Carcinoma, Non-Small-Cell Lung; Cell Line, Tumor; Autophagy; Animals; Humans; Smad3 Protein; Cell Proliferation; Signal Transduction

Non-small cell lung cancer (NSCLC) has the highest mortality rate among all solid tumors with a poor prognosis. The BMP and activin receptor membrane bound inhibitor (BAMBI) has been identified as a hallmark of NSCLC and β-sitosterol possesses antitumor potentiality. This study explores the effect of BAMBI overexpression and β-sitosterol in the context of NSCLC. The results revealed that the transfection of pcDNA‑BAMBI and β-sitosterol treatment significantly reduced the levels of autophagy markers light chain 3 (LC3) II and Beclin 1, whereas the levels of LC3 I and p62 were promoted. The reduced punctate accumulations of GFP-LC3 were detected in pcDNA-BAMBI and β-sitosterol groups, especially in pcDNA-BAMBI + β-sitosterol group. BAMBI overexpression and β-sitosterol induced G0/G1 cell cycle arrest and inhibted cell proliferation in A549 cells. In addition, the levels of transforming growth factor-β (TGF‑β)/p-Smad2/3/c-Myc pathway proteins were decreased. The TGF-β overexpression further confirmed that BAMBI overexpression and β-sitosterol treatment suppre-ssed autohagy and viability of A549 cells was through TGF-β/Smad2/3/c-Myc pathway. Finally, the tumor growth was suppressed in NSCLC xenografts, and the inhibitory effect was stronger under treatment of pcDNA-BAMBI toge-ther with β-sitosterol. These results indicate that BAMBI overexpression and β-sitosterol may serve as novel targets for the treatment of NSCLC.