MEK activation suppresses CPT11-induced apoptosis in rat intestinal epithelial cells through a COX-2-dependent mechanism

Youhei Horikawa, Michiro Otaka, Koga Komatsu, Mario Jin, Masaru Odashima, Isao Wada, Tamotsu Matsuhashi, Reina Ohba, Jinko Oyake, Natsumi Hatakeyama, Raymond N. DuBois, Sumio Watanabe

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Resistance to chemotherapeutic agents is one of the distinct features of cancer cells. We evaluate the role of activated MEK-ERK signaling in Camptotecin/irinotecan (CPT-11)-induced cell death using constitutively activated MEK1-transfected normal rat intestinal epithelial cells (IEC-caMEK cells). A CPT-11-induced inhibitory concentration of 50% was determined by WST assay. Apoptosis was evaluated by DNA staining and fragmented DNA analysis. Protein expressions were analyzed by western blotting. We also examined the role of cyclooxygenase-2 in the cell systems. IEC-caMEK cells possessed survival advantages compared to control cells. Apoptosis was remarkably suppressed in IEC-caMEK cells. Western blot analysis revealed increased expression of Bcl-2, Bcl-xL, Mcl-1, and COX-2 and decreased expression of Bak in IEC-caMEK cells. The COX-2 selective inhibitor ameliorated the antiapoptotic nature of IEC-caMEK cells. MEK activation suppressed CPT-11-induced apoptosis in IEC-caMEK cells via a COX-2- dependent mechanism. Therefore, MEK-ERK signaling may contribute to the drug-resistant nature of cancer cells.

Original languageEnglish (US)
Pages (from-to)2757-2765
Number of pages9
JournalDigestive Diseases and Sciences
Volume52
Issue number10
DOIs
StatePublished - Oct 2007
Externally publishedYes

Keywords

  • Apoptosis
  • COX-2
  • Chemotherapeutic agents
  • MEK-ERK signaling

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

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