Mechanism of resistance to chemoradiation in p53 mutant human colon cancer

Junichiro Hiro, Yasuhiro Inoue, Yuji Toiyama, Chikao Miki, Masato Kusunoki

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)


To understand one of the mechanisms of resistance to chemoradiation in colon cancer cells, we investigated whether 5-fluorouracil (5-FU) mediated the expression of epidermal growth factor receptor (EGFR) and modified repair of radiation-induced DNA damage, especially in a p53 independent pathway. Cytotoxicity was determined for 5-FU combined with radiation for three colon cancer cell lines that contain mutant p53 (SW480, HT29 and WiDr), using the WST-8 colorimetric assay. EGFR and the excision repair cross complementation group 1 (ERCC1) proteins during chemoradiation were measured by Western blot analysis. SW480 cells were significantly resistant to chemoradiation compared to the other mutant p53 cell lines. The alteration of EGFR and ERCC1 proteins during chemoradiation in SW480 was apparently inversely related to that of the other radiosensitive cell lines. 5-FU-induced activation of EGFR followed by radiation in SW480 cells resulted in up-regulation of ERCC1. In contrast, 5-FU-induced degradation of EGFR followed by radiation in the other radiosensitive cell lines resulted in down-regulation of ERCC1. This suggested a complementary interaction between EGFR and ERCC1, and that 5-FU-induced EGFR activation conferred protection against radiation, through activation of DNA repair. Interaction of EGFR and ERCC1 might correlate with radiation-induced DNA damage when p53 mutant colon cancer cell lines are exposed to 5-FU followed by radiation.

Original languageEnglish
Pages (from-to)1305-1310
Number of pages6
JournalInternational journal of oncology
Issue number6
Publication statusPublished - 06-2008
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research


Dive into the research topics of 'Mechanism of resistance to chemoradiation in p53 mutant human colon cancer'. Together they form a unique fingerprint.

Cite this