Resveratrol Inhibits Non-small Cell Lung Cancer via Directly Targeting EGFR and c-Met Signaling Pathways

Objective To investigate the mechanism of resveratrol-mediated inhibition effect on human non-small cell lung cancer.

Methods Non-small cell lung cancer cells were treated with various concentrations of resveratrol for 24, 48 and 72 h, the proliferation was evaluated by MTS and soft agar assay. Meanwhile, the activation of EGFR and c-Met signaling pathways after resveratrol treatment was tested via immunoblotting. The subcellular localization of EGFR and c-Met were assessed by Western blot. Flow cytometry was conducted to detect cell cycle progression.

Results Resveratrol inhibited the proliferation of non-small cell lung cancer cells in a dose-dependent manner. Moreover, resveratrol treatment not only suppressed the phosphorylation of EGFR and c-Met signaling pathways, but also resulted in the down-regulation of total EGFR protein expression level, as well as its localization on membrane and in nucleus. Additionally, resveratrol treatment decreased c-Met expression on membrane and inhibited the 60 kD cleaved variant of c-Met translocated into nucleus. Flow cytometry data demonstrated that resveratrol induced cell cycle G₀/G₁ arrest.

Conclusion Resveratrol inhibits human non-small cell lung cancer via directly targeting EGFR and c-Met signaling pathways.