Antitumour efficacy of MEK inhibitors in human lung cancer cells and their derivatives with acquired resistance to different tyrosine kinase inhibitors
2011

Effect of MEK Inhibitors on Lung Cancer Cells with Drug Resistance

publication Evidence: high

Author Information

Author(s): Morgillo F, Cascone T, D'Aiuto E, Martinelli E, Troiani T, Saintigny P, De Palma R, Heymach J V, Berrino L, Tuccillo C, Ciardiello F

Primary Institution: Seconda Università degli Studi di Napoli

Hypothesis

The study aims to investigate the molecular mechanisms regulating cancer cell resistance to four different tyrosine kinase inhibitors.

Conclusion

Resistance to four different TKIs is characterized by epithelial to mesenchymal transition (EMT), which is sensitive to MEK inhibitors in human CALU-3 lung adenocarcinoma.

Supporting Evidence

  • All four TKI-R CALU-3 cells showed increased invasion, migration and anchorage-independent growth.
  • Treatment with MEK inhibitors caused inhibition of cell proliferation and tumor growth in vivo.
  • Significant increase in the expression of activated, phosphorylated MET, IGF-1R, AKT, MEK, MAPK and survivin was observed in TKI-R CALU-3 cells.

Takeaway

The study found that lung cancer cells can become resistant to certain drugs, but using MEK inhibitors can help stop their growth.

Methodology

An in vitro model of acquired resistance was developed using the CALU-3 lung adenocarcinoma cell line, with various assays conducted to assess cell proliferation, migration, and invasion.

Statistical Information

P-Value

p<0.001

Statistical Significance

p<0.001

Digital Object Identifier (DOI)

10.1038/bjc.2011.244

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