Recombined humanized endostatin-induced suppression of HMGB1 expression inhibits proliferation of NSCLC cancer cells

Thorac Cancer. 2019 Jan;10(1):90-95. doi: 10.1111/1759-7714.12905. Epub 2018 Nov 28.

Abstract

Background: Recombined humanized endostatin (Rh-endostatin) exhibits a potent anti-cancer effect involving multiple molecular targets and signaling pathways. HMGB1 is a highly conserved DNA-binding protein involved in cancer development. The therapeutic effect of Rh-endostatin on HMGB1 has not been reported, thus we investigate the effect in non-small cell lung cancer (NSCLC) cells.

Methods: Quantitative real-time PCR and Western blot were used to analyze the messenger RNA and protein expression of HMGB1 in A549 cancer cells, while enzyme-linked immunosorbent assay was used to detect the release of HMGB1. Western blot was performed to evaluate HMGB1 expression in SK-MES-1 and H661 NSCLC cells.

Results: Rh-endostatin inhibited the proliferation of A549 cancer cells and distinctly downregulated the expression and release of HMGB1 in dose and time dependent manners. Rh-endostatin-induced HMGB1 downregulation was confirmed in different types of NSCLC cells.

Conclusion: These results demonstrate the general phenomenon that Rh-endostatin can induce HMGB1 suppression in a variety of NSCLC cells. Rh-endostatin may suppress HMGB1 expression and release in A549 cancer cells, thus inhibiting cell proliferation.

Keywords: Cell proliferation; HMGB1; NSCLC; recombined humanized endostatin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Apoptosis / drug effects
  • Carcinoma, Non-Small-Cell Lung / drug therapy*
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Proliferation / drug effects
  • Endostatins / genetics
  • Endostatins / pharmacology*
  • Gene Expression Regulation, Neoplastic / drug effects
  • HMGB1 Protein / antagonists & inhibitors
  • HMGB1 Protein / genetics*
  • Humans
  • Recombinant Proteins / genetics
  • Recombinant Proteins / pharmacology*
  • Signal Transduction / drug effects

Substances

  • Endostatins
  • HMGB1 Protein
  • HMGB1 protein, human
  • Recombinant Proteins