Liao Xiaozhong, Tao Lanting, Guo Wei, Wu Zhuo-Xun, Du Haiyan, Wang Jing, Zhang Jue, Chen Hanrui, Chen Zhe-Sheng, Lin Lizhu, Sun Lingling
Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.
Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, NY, United States.
Front Oncol. 2020 Sep 7;10:1732. doi: 10.3389/fonc.2020.01732. eCollection 2020.
The application of apatinib is immensely limited by its acquired drug resistance. This research investigates whether cordycepin, a component from Cordyceps could synergize with apatinib to improve its anticancer effect on non-small cell lung cancer (NSCLC) cells.
The NSCLC cell lines A549, PC9, and H1993, and human bronchial epithelial (HBE) cell line Bears-2B were used in this study. Cell counting kit 8, colony formation assays, wound healing assay, transwell assay, and flow cytometry analysis were performed to assess the cell viability, the migration ability, and invasion ability of the cells. Kyoto encyclopedia of genes and genomes (KEGG), western blotting and molecular docking was applied to analyze the possible pathways affected by cordycepin.
The combination of cordycepin and apatinib in a ratio of 5:1 synergistically reduced proliferation of NSCLC cells, inhibited cell migration and invasion, increased cell apoptosis by altering cell cycle in NSCLC A549 and PC9 cells. The VEGF/PI3K/Akt pathway was inhibited after treatment with cordycepin and apatinib.
Our findings demonstrated that the combination of cordycepin and apatinib has synergistically anticancer effect on NSCLC cells by down-regulating VEGF/PI3K/Akt signaling pathway. This result indicated that cordycepin and apatinib could be a promising drug combination against NSCLC.
阿帕替尼的应用受到其获得性耐药性的极大限制。本研究调查了冬虫夏草的一种成分虫草素是否能与阿帕替尼协同作用，以提高其对非小细胞肺癌（NSCLC）细胞的抗癌效果。
本研究使用了NSCLC细胞系A549、PC9和H1993，以及人支气管上皮（HBE）细胞系Bears-2B。进行细胞计数试剂盒8、集落形成试验、伤口愈合试验、Transwell试验和流式细胞术分析，以评估细胞的活力、迁移能力和侵袭能力。应用京都基因与基因组百科全书（KEGG）、蛋白质印迹法和分子对接来分析虫草素可能影响的途径。
虫草素与阿帕替尼以5:1的比例联合使用可协同降低NSCLC细胞的增殖，抑制细胞迁移和侵袭，通过改变NSCLC A549和PC9细胞的细胞周期增加细胞凋亡。用虫草素和阿帕替尼处理后，VEGF/PI3K/Akt通路受到抑制。
我们的研究结果表明，虫草素与阿帕替尼联合使用通过下调VEGF/PI3K/Akt信号通路对NSCLC细胞具有协同抗癌作用。这一结果表明，虫草素和阿帕替尼可能是一种有前景的抗NSCLC药物组合。
