Combination of DN604 with gemcitabine led to cell apoptosis and cell motility inhibition via p38 MAPK signaling pathway in NSCLC.

Non-small-cell lung cancer (NSCLC) is the most common cancer in the world, which is still treated with Pt(II) agents as first-line drugs. As a traditional anticancer agent, gemcitabine is usually used in the combination treatment of various solid tumors with other drugs. Here, we investigate the combinatory application of gemcitabine with a Pt(II) agent (DN604, reported previously in our former research) in the treatment of NSCLC. In vitro biological assays suggested that DN604-gemcitabine treatment can effectively induce cell apoptosis and suppress cell motility, showing better anti-tumor effect than the single drug treatment or the combined treatment of cisplatin and gemcitabine. More importantly, investigation on the mechanism of the combined treatment proved that such combined treatment can suppress cell autophagy to inhibit cell motility via the activation of p38 MAPK signaling pathway. In vivo studies indicated that combination of DN604 with gemcitabine significantly inhibited the growth of tumor with nearly no influence on the normal organs and weight of mice. Our study widened the application scope of Pt(II) agents combined with gemcitabine for NSCLC treatment.