Xiyuan Hospital, China Academy of Chinese Medical Sciences, Haidian, Beijing, 100091, People's Republic of China.
Xiyuan Hospital, China Academy of Chinese Medical Sciences, Haidian, Beijing, 100091, People's Republic of China.
Biomed Pharmacother. 2018 Dec;108:941-951. doi: 10.1016/j.biopha.2018.09.124. Epub 2018 Sep 27.
An-te-xiao capsule consists of total alkaloids from the dried whole plantof Solanum lyratum, and showed antitumor effects in our previous study. However, its inhibitory effect on multiple non-small cell lung cancer (NSCLC) cell lines and the underlying mechanisms have not been elucidated clearly. This study sought to investigate the inhibitory effects of An-te-xiao capsule on three main types of NSCLC cell lines (A549, NCI-H460, and NCI-H520) in vitro and in vivo and the underlying mechanisms of action including its potential anti-angiogenesis effects. An-te-xiao capsule showed no acute oral toxicity in mice, and significantly prolonged survival time in a mouse model of Lewis tumor xenograft. The inhibition of A549, NCI-H460, and NCI-H520 cells by An-te-xiao capsule was reflected in its effects on tumor growth, histopathological changes, tumor microvessel density (MVD), cell cycle regulatory proteins, and cell apoptosis. In vitro, An-te-xiao capsule repressed migration, invasion, and tube formation of tumor-derived vascular endothelial cells (Td-ECs), which were obtained using a co-culture system, in the presence or absence of vascular endothelial growth factor (VEGF) at safe concentrations selected using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Moreover, An-te-xiao capsule inhibited the secretion of VEGF by A549 cells in the co-culture system and suppressed the phosphorylation of VEGF receptor 2 (VEGFR2). Taken together, An-te-xiao capsule has potential for treating NSCLC.
安替胶囊由白花丹全草总生物碱组成,在我们之前的研究中显示出抗肿瘤作用。然而,其对多种非小细胞肺癌(NSCLC)细胞系的抑制作用及其作用机制尚未阐明。本研究旨在探讨安替胶囊在体外和体内对三种主要类型的 NSCLC 细胞系(A549、NCI-H460 和 NCI-H520)的抑制作用及其作用机制,包括其潜在的抗血管生成作用。安替胶囊在小鼠中无急性口服毒性,在 Lewis 肿瘤异种移植小鼠模型中显著延长了生存时间。安替胶囊对 A549、NCI-H460 和 NCI-H520 细胞的抑制作用反映在其对肿瘤生长、组织病理学变化、肿瘤微血管密度(MVD)、细胞周期调节蛋白和细胞凋亡的影响上。在体外,安替胶囊抑制了在安全浓度的血管内皮生长因子(VEGF)存在或不存在的情况下,使用共培养系统获得的肿瘤衍生血管内皮细胞(Td-ECs)的迁移、侵袭和管形成,该安全浓度是通过 3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐(MTT)测定法选择的。此外,安替胶囊抑制了 A549 细胞在共培养系统中的 VEGF 分泌,并抑制了 VEGF 受体 2(VEGFR2)的磷酸化。总之,安替胶囊具有治疗 NSCLC 的潜力。