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01.10.2007 | Original Paper

MEK Activation Suppresses CPT11-Induced Apoptosis in Rat Intestinal Epithelial Cells Through a COX-2-Dependent Mechanism

verfasst von: 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

Erschienen in: Digestive Diseases and Sciences | Ausgabe 10/2007

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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.

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Titel: MEK Activation Suppresses CPT11-Induced Apoptosis in Rat Intestinal Epithelial Cells Through a COX-2-Dependent Mechanism
verfasst von: 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
Publikationsdatum: 01.10.2007
Verlag: Springer US
Erschienen in: Digestive Diseases and Sciences / Ausgabe 10/2007
Print ISSN: 0163-2116
Elektronische ISSN: 1573-2568
DOI: https://doi.org/10.1007/s10620-007-9798-0

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