Lung cancer is a major public health problem worldwide. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases. Autophagy has recently sparked great interest, and it is thought to participate in a variety of diseases, including lung cancer. Uncoordinated (Unc) 51-like kinase 1 (Ulk1), a serine/threonine kinase, plays a central role in the autophagy pathway. However, the role of Ulk1 in NSCLC remains unclear. We report that NSCLC cell lines exhibited high expression of Ulk1 and that Ulk1 was negatively correlated with prognosis in lung cancer patients. Knockdown of Ulk1 or the inhibition of Ulk1 by the selective inhibitor SBI0206965, inhibited cell proliferation, induced cell apoptosis and enhanced the sensitivity of cisplatin against NSCLC cells. Moreover, we demonstrated that Ulk1 exerted oncogenic activity in NSCLC by modulating both autophagy and apoptosis pathways. Inhibition of autophagy by SBI0206965 sensitized NSCLC cells to cisplatin by inhibiting cisplatin induced cell-protective autophagy to promote apoptosis. Furthermore, SBI0206965 promoted apoptosis in NSCLC cells independent of autophagy, which was partly mediated by destabilization of Bcl2/Bclxl. In summary, our results show that inhibition of Ulk1 suppresses NSCLC cell growth and sensitizes NSCLC cells to cisplatin by modulating both autophagy and apoptosis pathways, and that Ulk1 might be a promising target for NSCLC treatment.

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Berberine is a plant-derived compound used in traditional Chinese medicine, which has been shown to inhibit cell proliferation and migration in breast cancer. On the other hand, vasodilator-stimulated phosphoprotein (VASP) promotes actin filament elongation and cell migration. We previously showed that VASP is overexpressed in high-motility breast cancer cells. Here we investigated whether the anti-tumorigenic effects of berberine are mediated by binding VASP in basal-like breast cancer. Our results show that berberine suppresses proliferation and migration of MDA-MB-231 cells as well as tumor growth in MDA-MB-231 nude mouse xenografts. We also show that berberine binds to VASP, inducing changes in its secondary structure and inhibits actin polymerization. Our study reveals the mechanism underlying berberine's inhibition of cell proliferation and migration in basal-like breast cancer, highlighting the use of berberine as a potential adjuvant therapeutic agent.

Histone deacetylases (HDACs) are promising targets for cancer therapy, and first-generation HDAC inhibitors are currently in clinical trials for the treatment of cancer patients. HDAC6, which is a key regulator of many signaling pathways that are linked to cancer, has recently emerged as an attractive target for the treatment of cancer. In the present study, HDAC6 was found to be overexpressed in lung adenocarcinoma cell lines and was negatively correlated with the prognosis of patients with lung adenocarcinoma. Overexpression of HDAC6 promoted the proliferation of lung adenocarcinoma cells in a deacetylase activity-dependent manner. HDAC6 overexpression conferred resistance to gefitinib via the stabilization of epidermal growth factor receptor (EGFR). The inhibition of HDAC6 by CAY10603, a potent and selective inhibitor of HDAC6, inhibited the proliferation of lung adenocarcinoma cells and induced apoptosis. CAY10603 downregulated the levels of EGFR protein, which in turn inhibited activation of the EGFR signaling pathway. Moreover, CAY10603 synergized with gefitinib to induce apoptosis of the lung adenocarcinoma cell lines via the destabilization of EGFR. Taken together, our results suggest that the inhibition of HDAC6 may be a promising strategy for the treatment of lung adenocarcinoma.