sirolimus and apatinib

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.. 【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】.

Topics: Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Movement; Cell Proliferation; Dose-Response Relationship, Drug; Drug Interactions; Humans; Lung Neoplasms; Pyridines; Sirolimus; Small Cell Lung Carcinoma