Liu Chao, Zhang Hongbing, Li Yongwen, Zhang Zihe, Shi Ruifeng, Xu Songlin, Zhu Guangsheng, Wang Pan, Liu Hongyu, Chen Jun
Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, Tianjin 300052, China.
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Zhongguo Fei Ai Za Zhi. 2020 Apr 20;23(4):216-222. doi: 10.3779/j.issn.1009-3419.2020.104.08. Epub 2020 Mar 26.
Lung cancer is the most common malignancy world-wide. Small cell lung cancer is the deadliest subtype of lung cancer, which features such as rapid growth, early metastasis, and high vascularization. Apatinib is a vascular endothelial growth factor receptor 2 inhibitor independently developed in China, which has a significant inhibition in a variety of solid tumors. The purpose of this study is to investigate the effects of Apatinib alone or Apatinib combined with mammalian target of rapamycin (mTOR) inhibitor, CCI-779, on small cell lung cancer cell line NCI-H446 in vitro.
The small cell lung cancer cell line NCI-H446 was grew in vitro. The effects of Apatinib alone or Apatinib combined with CCI-779 on proliferation, apoptosis, cell cycle and migration of NCI-H446 small cell lung cancer cells were detected by CCK8; FACS and transwell assays were also carried out; Western blot assays were used to detect vascular endothelial growth factor and cell cycle related protein expression.
CCK8 assays showed that high concentration of Apatinib could inhibit the proliferation of NCI-H446 cells. Apoptosis assays showed that high concentration of Apatinib could induce NCI-H446 cell apoptosis. Transwell assays showed that high concentration of Apatinib could inhibit NCI-H446 cell migration. After combined with mTOR inhibitor CCI-779, low concentration of Apatinib could inhibit the proliferation and migration of NCI-H446 small cell lung cancer cells and induce apoptosis.
Apatinib has a concentration-dependent effect on the small cell lung cancer cell line NCI-H446. High concentration of Apatinib can inhibit the proliferation and migration of NCI-H446 small cell lung cancer cells, induce apoptosis. Apatinib combined with the mTOR inhibitor CCI-779 can sensitize the NCI-H446 cells to Apatinib.
肺癌是全球最常见的恶性肿瘤。小细胞肺癌是肺癌中最致命的亚型，具有生长迅速、早期转移和高血管化等特征。阿帕替尼是我国自主研发的一种血管内皮生长因子受体2抑制剂，对多种实体瘤有显著抑制作用。本研究旨在探讨阿帕替尼单独使用或与雷帕霉素靶蛋白（mTOR）抑制剂CCI-779联合使用对小细胞肺癌细胞系NCI-H446的体外作用。
小细胞肺癌细胞系NCI-H446在体外培养。采用CCK8检测阿帕替尼单独使用或与CCI-779联合使用对NCI-H446小细胞肺癌细胞增殖、凋亡、细胞周期和迁移的影响；同时进行流式细胞术（FACS）和Transwell实验；采用蛋白质免疫印迹法检测血管内皮生长因子和细胞周期相关蛋白表达。
CCK8实验表明，高浓度阿帕替尼可抑制NCI-H446细胞增殖。凋亡实验表明，高浓度阿帕替尼可诱导NCI-H446细胞凋亡。Transwell实验表明，高浓度阿帕替尼可抑制NCI-H446细胞迁移。与mTOR抑制剂CCI-779联合使用后，低浓度阿帕替尼即可抑制NCI-H446小细胞肺癌细胞增殖和迁移并诱导凋亡。
阿帕替尼对小细胞肺癌细胞系NCI-H446具有浓度依赖性作用。高浓度阿帕替尼可抑制NCI-H446小细胞肺癌细胞增殖和迁移，诱导凋亡。阿帕替尼与mTOR抑制剂CCI-779联合使用可使NCI-H446细胞对阿帕替尼敏感。
