In vivo and in vitro effects of hyperplasia suppressor gene on the proliferation and apoptosis of lung adenocarcinoma A549 cells

Biosci Rep. 2018 Oct 2;38(5):BSR20180391. doi: 10.1042/BSR20180391. Print 2018 Oct 31.

Abstract

Lung adenocarcinoma is the most common subtype of non-small cell lung cancer (NSCLC). Hyperplasia suppressor gene (HSG) has been reported to inhibit cell proliferation, migration, and remodeling in cardiovascular diseases. However, there lacks systematic researches on the effect of HSG on the apoptosis and proliferation of lung adenocarcinoma A549 cells and data of in vivo experiments. The present study aims to investigate the effects of HSG gene silencing on proliferation and apoptosis of lung adenocarcinoma A549 cells. The human lung adenocarcinoma A549 cell was selected to construct adenovirus vector. Reverse transcription-quantitative PCR (RT-qPCR) and Western blot analysis were conducted to detect expressions of HSG and apoptosis related-proteins. Cell Counting Kit (CCK)-8 assay was performed to assess A549 cell proliferation and flow cytometry to analyze cell cycle and apoptosis rate. The BALB/C nude mice were collected to establish xenograft model. Silenced HSG showed decreased mRNA and protein expressions of HSG, and elevated A549 cell survival rates at the time point of 24, 48, and 72 h. The ratio of cells at G0/G1 phase and apoptosis rate decreased and the ratio of cells at S- and G2/M phases increased following the silencing of HSG. There were decreases of B cell lymphoma-2 (Bcl-2)-associated X protein (Bax), Caspase-3, and Caspase-8 expressions but increases in Bcl-2 induced by silenced HSG. As for the xenograft in nude mice, tumor volume increased, and apoptosis index (AI) decreased after HSG silencing. These results indicate that HSG gene silencing may promote the proliferation of A549 cells and inhibit the apoptosis. HSG may be a promising target for the treatment of lung adenocarcinoma.

Keywords: A549 cells; Apoptosis; Gene silencing; Hyperplasia suppressor gene; Lung adenocarcinoma; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • A549 Cells
  • Adenocarcinoma of Lung / genetics
  • Adenocarcinoma of Lung / pathology*
  • Animals
  • Apoptosis / genetics
  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase 8 / genetics
  • Caspase 8 / metabolism
  • Cell Proliferation / genetics
  • Female
  • GTP Phosphohydrolases / genetics*
  • GTP Phosphohydrolases / metabolism
  • Gene Silencing
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / pathology*
  • Mice, Inbred BALB C
  • Mitochondrial Proteins / genetics*
  • Mitochondrial Proteins / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Xenograft Model Antitumor Assays
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAX protein, human
  • Mitochondrial Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • CASP3 protein, human
  • CASP8 protein, human
  • Caspase 3
  • Caspase 8
  • GTP Phosphohydrolases
  • MFN2 protein, human