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Silencing of the type 1 insulin-like growth factor receptor increases the sensitivity to apoptosis and inhibits invasion in human lung adenocarcinoma A549 cells

Abstract

The type 1 insulin-like growth factor receptor (IGF-1R), which is over-expressed or activated in many human cancers, including lung cancer, mediates cancer cell proliferation and metastasis. Several studies indicate that blocking IGF-1R expression can inhibit tumor cell proliferation and metastasis. In this study, inhibition of the endogenous IGF-1R by recombinant adenoviruses encoding short hairpin RNAs against IGF-1R was found to significantly suppress IGF-1R expression, arrest the cell cycle, enhance the apoptotic response, and inhibit proliferation, adhesion, invasion and migration in A549 cells. Moreover, silencing IGF-1R decreases the expression of invasive-related genes including matrix metalloproteinase-2 (MMP-2), MMP-9, and urokinase-plasminogen activator (u-PA), and the phosphorylation of Akt and ERK1/2. These results suggest that the silencing of IGF-1R has the potential to be an effective cancer gene therapy strategy for human lung cancer.

Abbreviations

ECM:

extracellular matrix

HRP:

horseradish peroxidise

IGF-1R:

type 1 insulin-like growth factor receptor

McAb:

monoclonal antibody

MMP:

matrix metalloproteinase

NSCLC:

non-small cell lung cancer

PcAb:

polyclonal antibody

shRNA:

short hairpin RNA

u-PA:

urokinase-plasminogen activator

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Correspondence to Aiqiang Dong.

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Ma, Z., Dong, A., Kong, M. et al. Silencing of the type 1 insulin-like growth factor receptor increases the sensitivity to apoptosis and inhibits invasion in human lung adenocarcinoma A549 cells. Cell Mol Biol Lett 12, 556–572 (2007). https://doi.org/10.2478/s11658-007-0022-1

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Key words

  • IGF-1R
  • Lung cancer
  • Short hairpin RNA
  • MMPs
  • Apoptosis
  • Metastasis