Epidermal growth factor-induced cell death and radiosensitization in epidermal growth factor receptor-overexpressing cancer cell lines

Kyubo Kim, Hong Gyun Wu, Sang Rok Jeon

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Background/Aim: The aim of the present study was to suggest potential mechanisms of epidermal growth factor (EGF)-induced cell death and radiosensitization in EGF receptor (EGFR)-overexpressing cancer cell lines.

Materials and Methods: Two EGFR-overexpressing cancer cell lines (AMC-HN3, and A431), one EGFR-null cancer cell line (H520) and normal fibroblasts were cultured with 0.01-1000 nM of recombinant human EGF (rhEGF), and a clonogenic assay was performed. After culturing serum-starved cells with 10 nM rhEGF, the expression patterns of two apoptosis-associated proteins (cleaved caspase-3 and cleaved poly(ADP-ribose) polymerase (PARP)) and the phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR) signaling pathway were measured using immunoblotting. The radiosensitizing effect of EGF was also evaluated with a clonogenic assay and phosphorylated H2AX (γH2AX) immunofluorescence.

Results: In the clonogenic assay, the number of colonies was decreased in a dose-dependent manner in EGFR-overexpressing cancer cell lines. The expression of cleaved caspase-3 and cleaved PARP was significantly induced in EGFR-overexpressing cancer cell lines. As for the PI3K/AKT/mTOR signaling pathway, EGF paradoxically suppressed the expression of PI3K, AKT and mTOR in a timedependent manner. As for the radiosensitizing effect, EGF enhanced the radiosensitivity of AMC-HN3 and A431 cells.

Conclusion: rhEGF treatment induced cell death in the two EGFR-overexpressing cancer cell lines, and the mode of cell death was apoptosis. Moreover, cell death might be associated with the paradoxical suppression of PI3K/AKT/mTOR signaling pathway. rhEGF in combination with radiation augmented the radiation effect in EGFR-overexpressing cancer cell lines via inhibition of DNA damage repair.

Original languageEnglish
Pages (from-to)245-254
Number of pages10
JournalAnticancer Research
Volume35
Issue number1
StatePublished - 1 Jan 2015

Keywords

  • Apoptosis
  • EGF
  • EGFR-overexpressing cancer cell line
  • PI3K/AKT/mTOR signaling pathway
  • Radiosensitization

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