The inhibitory effects of rh-endostatin (YH-16) in combination with radiotherapy on lung adenocarcinoma A549 in mice and the underlying mechanisms

J Huazhong Univ Sci Technolog Med Sci. 2010 Feb;30(1):108-12. doi: 10.1007/s11596-010-0120-6. Epub 2010 Feb 14.

Abstract

In order to investigate the inhibitory effects of Endostar (rh-endostatin, YH-16) in combination with radiotherapy on lung adenocarcinoma A549 in mice and the interaction mechanisms of combined therapy, the transplantation tumor models of A549 lung adenocarcinoma were established. When the largest diameter of tumor reached 1.0 cm, all nude mice were randomly divided into 4 groups: Endostar group, radiotherapy group, radiotherapy plus Endostar (combined treatment) group, and control group (n=6 in each group). The largest diameter and the vertical diameter of tumor were measured at different time points. At the 16th day, mice were executed, and the tumors were applied to analysis of rate of tumor cell apoptosis, and the expression levels of basic fibroblast growth factor (bFGF) mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR) and those of vascular endothelial growth factor (VEGF) by immunohistochemistry. The results demonstrated that the rate of tumor inhibition in combined treatment group was higher than that in other groups. And the rate of tumor cell apoptosis in combined treatment group was also higher than that in other groups. Meanwhile, the levels of bFGF mRNA and VEGF expression in combined treatment group were lower than those in other groups. It was concluded that Endostar obviously enhanced the curative effectiveness of radiotherapy on lung adenocarcinoma A549 in mice. The underlying mechanisms may involve the down-regulation of bFGF mRNA and VEGF expression to inhibit angiogenesis by Endostar and the cooperative effect of Endostar and radiotherapy to synergistically promote tumor cell apoptosis. And Endostar inhibits angiogenesis by down-regulating the expression of bFGF mRNA and VEGF.

MeSH terms

  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Cell Line, Tumor
  • Combined Modality Therapy
  • Down-Regulation
  • Endostatins / therapeutic use*
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism
  • Humans
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy*
  • Mice
  • Mice, Nude
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Radiotherapy*
  • Recombinant Proteins / therapeutic use
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Xenograft Model Antitumor Assays

Substances

  • Angiogenesis Inhibitors
  • Endostatins
  • RNA, Messenger
  • Recombinant Proteins
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • endostar protein