Tuberc Respir Dis.  2011 Oct;71(4):259-265.

Enhanced Sensitivity to Gefitinib after Radiation in Non-Small Cell Lung Cancer Cells

Affiliations
  • 1Department of Oncology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
  • 2Division of Pulmonology, Department of Internal Medicine, Korea Cancer Center Hospital, Seoul, Korea. cheol@kcch.re.kr

Abstract

BACKGROUND
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, gefitinib and erlotinib, are effective therapies for non-small cell lung cancer (NSCLC) patients whose tumors harbor somatic mutations in EGFR. The mutations are, however, only found in about 30% of Asian NSCLC patients and all patients ultimately develop resistance to these agents. Ionizing radiation has been shown to induce autophosphorylation of EGFR and activate its downstream signaling pathways. In the present study, we have tested whether the effect of gefitinib treatment can be enhanced after ionizing radiation.
METHODS
We compared the PC-9 and A549 cell line with its radiation-resistant derivatives after gefitinib treatment with cell proliferation and apoptosis assay. We also analyzed the effect of gefitinib after ionizing radiation in PC-9, A549, and NCI-H460 cells. Cell proliferation was determined by MTT assay and induction of apoptosis was evaluated by flow cytometry. Caspase 3 activation and PARP cleavage were evaluated by western blot analysis.
RESULTS
PC-9 cells having mutated EGFR and their radiation-resistant cells showed no significant difference in cell viability. However, radiation-resistant A549 cells were more sensitive to gefitinib than were their parental cells. This was attributable to an increased induction of apoptosis. Gefitinib-induced apoptosis increased significantly after radiation in cells with wild type EGFR including A549 and NCI-H460, but not in PC-9 cells with mutated EGFR. Caspase 3 activation and PARP cleavage accompanied these findings.
CONCLUSION
The data suggest that gefitinib-induced apoptosis could increase after radiation in cells with wild type EGFR, but not in cells with mutated EGFR.

Keyword

gefitinib; Radiation; Carcinoma, Non-Small-Cell Lung

MeSH Terms

Apoptosis
Asian Continental Ancestry Group
Blotting, Western
Carcinoma, Non-Small-Cell Lung
Caspase 3
Cell Line
Cell Proliferation
Cell Survival
Flow Cytometry
Humans
Parents
Protein-Tyrosine Kinases
Quinazolines
Radiation, Ionizing
Receptor, Epidermal Growth Factor
Erlotinib Hydrochloride
Caspase 3
Protein-Tyrosine Kinases
Quinazolines
Receptor, Epidermal Growth Factor
Full Text Links
  • TRD
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
    DB Error: unknown error