Overexpression of pro-gastrin releasing peptide promotes the cell proliferation and progression in small cell lung cancer

Biochem Biophys Res Commun. 2016 Oct 14;479(2):312-318. doi: 10.1016/j.bbrc.2016.09.066. Epub 2016 Sep 15.

Abstract

Pro-gastrin releasing peptide (ProGRP) plays the role of oncogene in small cell lung cancer (SCLC). In this study, we aim to explore the biological function of ProGRP in SCLC cells and its potential mechanism. Expression of ProGRP in SCLC tissues and cell lines were detected by immunohistochemistry and western blot analysis, respectively. The transduced cell lines with ProGRP down-regulation were established using RNA interference technology. Cell viability, cologenic, apoptosis-associated assay and the biomarker levels determination for cell supernatant were performed in the transduced cells to elucidate the biological functions and mechanisms of ProGRP in SCLC cells. Our data showed that ProGRP protein was demonstrated a higher level in SCLC tissues and cells compared with the control, and its diagnostic efficiency was better than NSE, further, the higher levels of ProGRP were detected in the patients with extensive disease stage (P < 0.05), were also the unfavorable factor to the prognosis of SCLC patients. Additionally, the concentration of serum ProGRP is a useful biomarker in disease-monitoring of the patients with SCLC. Down-regulation of ProGRP significantly reduced SCLC cell growth, repressed colony formation, but increased cancer cell apoptosis. Additionally, repression of ProGRP also induced change in the cell cycle and output of NSE. Our data indicated that ProGRP serve as the useful biomarker in the management of SCLC and might be a potential therapeutic target.

Keywords: Apoptosis; Pro-gastrin releasing peptide; Proliferation; Small cell lung cancer.

MeSH terms

  • A549 Cells
  • Aged
  • Apoptosis*
  • Biomarkers, Tumor / metabolism
  • Case-Control Studies
  • Cell Cycle
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival
  • Down-Regulation
  • Female
  • Flow Cytometry
  • Gastrin-Releasing Peptide / metabolism*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Sensitivity and Specificity
  • Small Cell Lung Carcinoma / metabolism*

Substances

  • Biomarkers, Tumor
  • Gastrin-Releasing Peptide