Lung cancer is the worldwide leading cause of cancer-related death. Here, we described the synthesis and the anticancer activity of a novel coptisine derivative 8-cetylcoptisine (CCOP) on lung carcinoma in vitro and in vivo. CCOP inhibited the cell viability of A549, BGC-823, MDA-MB-231, HCT-116 and HepG2 cell lines. In A549 cells, CCOP induced apoptosis, G0/G1 cell cycle arrest and decreased mitochondrial membrane potential (MMP) in a dose-dependent manner. Western blot analysis showed that CCOP increased the expression of Bcl-2-associated X protein (Bax), cleaved caspase 3 and 9, while decreased B-cell lymphoma 2 (Bcl-2), cyclins D and E, cyclin dependent kinases (CDKs) 2, 4 and 6, along with the inactivation of the upstream phosphoinositide 3-kinase (Pi3k)/protein kinase B (Akt) signaling. Further in vivo studies showed that CCOP (10 mg/kg) significantly delayed tumor growth in A549 xenograft nude mice, which is stronger than that of coptisine (100 mg/kg). These data suggested that CCOP could be a candidate for lung cancer therapy.

肺癌是与癌症相关的死亡的全球主要诱因。在这里，我们描述的合成和对肺癌的新的黄连衍生物8- cetylcoptisine（CCOP）的抗癌活性的体外和体内。CCOP抑制了A549，BGC-823，MDA-MB-231，HCT-116和HepG2细胞系的细胞活力。在A549细胞中，CCOP以剂量依赖的方式诱导细胞凋亡，G0 / G1细胞周期停滞并降低线粒体膜电位（MMP）。蛋白质印迹分析表明，CCOP增加了Bcl-2相关X蛋白（Bax）的表达，裂解了caspase 3和9，同时降低了B细胞淋巴瘤2（Bcl-2），细胞周期蛋白D和E，细胞周期蛋白依赖性激酶（CDKs） 2、4和6），以及上游磷酸肌醇3激酶（Pi3k）/蛋白激酶B（Akt）信号的失活。进一步体内研究表明，CCOP（10 mg / kg）显着延迟了A549异种移植裸鼠的肿瘤生长，其强度比黄连碱（100 mg / kg）强。这些数据表明，CCOP可能是肺癌治疗的候选药物。