An-te-xiao capsule inhibits tumor growth in non-small cell lung cancer by targeting angiogenesis.

ABSTRACT

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.