Yang Jun, He Du, Peng Yan, Zhong Hongzhen, Deng Yuhong, Yu Zhonghua, Guan Chengnong, Zuo Yufang, Xu Zumin
Cancer Center, Affiliated Hospital of Guangdong Medical University, Zhanjiang.
Department of Oncology, the Central Hospital of Enshi Autonomous Prefecture, Enshi, China.
Onco Targets Ther. 2017 Oct 27;10:5209-5217. doi: 10.2147/OTT.S149609. eCollection 2017.
Non-small cell lung cancer (NSCLC) is the major cause of deaths among all the cancer types worldwide. Most of the NSCLC is diagnosed at an advanced stage and the 5-year overall survival rate is low. The reason for the low survival rate of patients with NSCLC is mainly due to distant metastasis. Matrine, a traditional Chinese medicine, has been shown a significant anti-proliferation and anti-invasive effect in tumors. However, little is known on the anti-invasive mechanism of matrine in lung cancer. Therefore, we tried to investigate the molecular mechanism of matrine on the invasive ability of NSCLC cells in vitro. Cell Counting Kit-8 assay was used to evaluate the cell viability. Transwell assay was used to detect the migration and invasion abilities. Microarray assay was used to analyze the differentiated expression genes with or without matrine treatment. Western blotting and real-time polymerase chain reaction were applied to detect the expressions of , E-cadherin and N-cadherin. Our study showed that matrine could suppress the proliferative activity of NSCLC cells in a dose- and time-dependent manner. Further investigation discovered that the migration and invasion of NSCLC cells were significantly inhibited by treatment with different concentrations of matrine. Microarray assay, real-time polymerase chain reaction and western blotting showed that matrine could significantly decrease the expression of PAX2. In addition, epithelial-mesenchymal transition and related proteins were decreased. In conclusion, matrine may block PAX2 expression to interfere with epithelial-mesenchymal transition signaling pathway that ultimately inhibit the migration and invasion of NSCLC cells in vitro. Matrine might serve as a potential agent for NSCLC treatment.
非小细胞肺癌（NSCLC）是全球所有癌症类型中导致死亡的主要原因。大多数NSCLC在晚期被诊断出来，5年总生存率较低。NSCLC患者生存率低的原因主要是远处转移。苦参碱是一种中药，已显示出对肿瘤具有显著的抗增殖和抗侵袭作用。然而，苦参碱在肺癌中的抗侵袭机制尚不清楚。因此，我们试图研究苦参碱对NSCLC细胞体外侵袭能力的分子机制。采用细胞计数试剂盒-8法评估细胞活力。采用Transwell法检测迁移和侵袭能力。采用基因芯片分析苦参碱处理与否的差异表达基因。应用蛋白质印迹法和实时聚合酶链反应检测 、E-钙黏蛋白和N-钙黏蛋白的表达。我们的研究表明，苦参碱能以剂量和时间依赖性方式抑制NSCLC细胞的增殖活性。进一步研究发现，不同浓度的苦参碱处理可显著抑制NSCLC细胞的迁移和侵袭。基因芯片分析、实时聚合酶链反应和蛋白质印迹法表明，苦参碱可显著降低PAX2的表达。此外，上皮-间质转化及相关蛋白减少。总之，苦参碱可能通过阻断PAX2表达来干扰上皮-间质转化信号通路，最终在体外抑制NSCLC细胞的迁移和侵袭。苦参碱可能成为治疗NSCLC的潜在药物。
