Aloperine inhibits the progression of non-small-cell lung cancer through the PI3K/Akt signaling pathway

Background: Lung Cancer has become the leading cause of cancer-related death worldwide and non-small-cell lung Cancer (NSCLC) accounts for approximately 85% of cases. Aloperine (ALO), an alkaloid active natural component from S. alopecuroide, has been found to exhibit anti-inflammatory, anti-tumor and anti-viral activity. However, Whether ALO exerts anti-tumor function on NSCLC remains poorly understood, and the underlying mechanisms remain unknown.

Methods: The CCK-8, colony formation, cell Apoptosis with flow cytometry, wound healing and transwell cell invasion assays, were used to analyze the tumor progression of H1299 and A549 cells treated with ALO in vitro, and the xenograft model was constructed to assess the effect of ALO in vivo. The expression of protein was detected by Western blotting.

Results: ALO suppressed the cell proliferation, self-renewal, migration and invasion, induced Apoptosis in A549 and H1299 cell. Furthermore, ALO significantly enhanced the level of cytochrome c in cytosol, and resulted in the dramatical increased levels of the cleaved Caspase-3, caspased-9 and PARP. ALO also inhibited the expression of MMP-2 and MMP-9. Additionally, ALO also reduced p-AKT and p-mTOR to attenuate the PI3K/Akt signaling pathway.

Conclusion: This study unveils a rationale for ALO through PI3K/Akt signaling pathway affecting the cell progression such as cell growth, Apoptosis and invasion, and ALO acts as a potential chemotherapeutic agent for NSCLC.