Background: 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.
Methods: 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.
Results: 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.
Conclusions: 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.
【中文题目：阿帕替尼联合CCI-779体外抑制小细胞肺癌细胞株NCI-H446的增殖和迁移】 【中文摘要：背景与目的 肺癌是世界上最常见的恶性肿瘤，其中小细胞肺癌是恶性程度最高的亚型，具有生长迅速、早期转移和高度血管化等特点。阿帕替尼（Apatinib）是我国自主研发的血管内皮生长因子受体2抑制剂，在多种实体瘤中疗效显著。本研究旨在探讨Apatinib对小细胞肺癌细胞株NCI-H446的体外作用以及联合哺乳动物雷帕霉素靶蛋白（mammalian target of rapamycin, mTOR）抑制剂CCI-779对小细胞肺癌的体外作用。方法 体外培养小细胞肺癌细胞株NCI-H446，CCK8法、细胞凋亡实验、细胞周期实验及Transwell实验检测Apatinib及联合mTOR抑制剂CCI-779对NCI-H446细胞增殖、凋亡、周期及迁移的影响；Western blot实验检测血管内皮生长因子受体和细胞周期相关蛋白的表达。结果 CCK8实验结果显示高浓度Apatinib能抑制NCI-H446细胞增殖；细胞凋亡实验结果显示高浓度Apatinib诱导NCI-H446细胞凋亡；Transwell实验结果显示高浓度Apatinib抑制NCI-H446细胞迁移；联合mTOR抑制剂CCI-779后，低浓度Apatinib便能抑制NCI-H446细胞增殖和迁移，诱导细胞凋亡。结论 Apatinib对小细胞肺癌细胞株NCI-H446的作用具有浓度依赖性特征，高浓度Apatinib能够抑制NCI-H446细胞增殖和迁移，诱导细胞凋亡，与mTOR抑制剂CCI-779联用能增加NCI-H446细胞对Apatinib的敏感性。】 【中文关键词：肺肿瘤；阿帕替尼；mTOR抑制剂；CCI-779；细胞周期；凋亡；细胞迁移】.
Keywords: Apatinib; Apoptosis; CCI-779; Cell cycle; Cell migration; Lung neoplasms; mTOR inhibitor.