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.

非小细胞肺癌（NSCLC）是世界上最常见的癌症，仍将Pt（II）药物作为一线药物进行治疗。作为传统的抗癌药，吉西他滨通常用于与其他药物联合治疗各种实体瘤。在这里，我们研究了吉西他滨与Pt（II）剂（DN604，先前在我们先前的研究中已有报道）的联合应用，用于NSCLC的治疗。体外生物学分析表明，DN604-吉西他滨治疗可有效诱导细胞凋亡并抑制细胞运动，与单药或顺铂和吉西他滨联合治疗相比，具有更好的抗肿瘤作用。更重要的是，对联合治疗机制的研究证明，这种联合治疗可以通过激活p38 MAPK信号通路抑制细胞自噬，从而抑制细胞运动。体内研究表明，DN604与吉西他滨的组合可显着抑制肿瘤的生长，而对小鼠的正常器官和体重几乎没有影响。我们的研究拓宽了Pt（II）药物联合吉西他滨在NSCLC治疗中的应用范围。