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

Biomed Pharmacother. 2018 Dec:108:941-951. doi: 10.1016/j.biopha.2018.09.124. Epub 2018 Sep 27.

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.

Keywords: An-te-xiao capsule; Angiogenesis; Non-small cell lung cancer; Solanum lyratum.

MeSH terms

  • A549 Cells
  • Alkaloids / pharmacology
  • Angiogenesis Inhibitors / pharmacology*
  • Animals
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Cell Line
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Drugs, Chinese Herbal / pharmacology*
  • Female
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Neovascularization, Pathologic / drug therapy*
  • Neovascularization, Pathologic / metabolism
  • Phosphorylation / drug effects
  • Signal Transduction / drug effects
  • Solanum / chemistry
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays / methods

Substances

  • Alkaloids
  • Angiogenesis Inhibitors
  • Drugs, Chinese Herbal
  • Vascular Endothelial Growth Factor A