Modulation of Ionizing Radiation-Induced G2 Arrest by Cyclooxygenase-2 and its Inhibitor Celecoxib

Hyun Jung Jun, Young Mee Kim, Soo Yeon Park, Ji Sun Park, Eun Jung Lee, Shin Ae Choi, Hongryull Pyo

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Purpose: Prolongation or attenuation of ionizing radiation (IR)-induced G2-M arrest in cyclooxygenase-2 (COX-2) overexpressing or celecoxib-treated cells, respectively, has been previously observed. To better understand the molecular mechanisms involved, we investigated the molecules involved in G2 checkpoint pathways after treatment with IR ± celecoxib. Methods and Materials: Various molecules in the G2 checkpoint pathways were investigated in HCT-116-Mock and -COX-2 cells. Western blot, reverse transcriptase polymerase chain reaction, confocal microscopy, and fluorescence activated cell sorter (FACS) analyses were performed to investigate whether expression and activity of the ataxia telangiectasia and rad3-related (ATR) could be modulated by COX-2 and its selective inhibitors. Results: COX-2 overexpression increased expression and activity of ATR after IR exposure. Celecoxib downregulated ATR in all tested cell lines independent of COX-2 expression, but downregulation was greater in COX-2 overexpressing cells after cells were irradiated. Celecoxib pretreatment before radiation caused strongly inhibited G2 arrest. Conclusions: COX-2 appears to prolong IR-induced G2 arrest by upregulating ATR. Celecoxib downregulated ATR preferentially in irradiated COX-2 overexpressing cells. Celecoxib may radiosensitize cancer cells by inhibiting G2 arrest through ATR downregulation.

Original languageEnglish (US)
Pages (from-to)225-234
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume75
Issue number1
DOIs
StatePublished - Sep 1 2009

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Keywords

  • ATR
  • COX-2
  • G arrest
  • celecoxib
  • radiation

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

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