Abstract B71: Chemosensitization to bleomycin conferred by a constitutive activation of IKK pathway in viral FLIP expressing cells
| Autor: | Kohji Noguchi, Junko Mitsuhashi, Kazuhiro Katayama, Yoshikazu Sugimoto, Yuri Masuda |
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| Rok vydání: | 2009 |
| Předmět: | |
| Zdroj: | Molecular Cancer Therapeutics. 8:B71-B71 |
| ISSN: | 1538-8514 1535-7163 |
| DOI: | 10.1158/1535-7163.targ-09-b71 |
| Popis: | Chemosensitivity to anticancer drugs is influenced by various gene expressions in a variety of cancer cell types. Identification of gene affecting chemotherapeutic efficacy should contribute to design of optimized therapeutic strategy for cancer. IkappaB kinase (IKK) complex activates NF-kappaB pathway, and NF-kappaB activation causes complicated effects on cell proliferation, survival, apoptosis and chemosensitivity through induction of various gene expressions such as antiapoptotic genes. To address an effect of IKK complex activation on cancer cell chemosensitivity, viral FLIP (vFLIP/K13/ORF71) encoded by Kaposi sarcoma-associated virus/Human herpes virus-8 (KSHV/HHV-8) was stably expressed in HEK293 cells. Viral FLIP activates IKK complex by a direct binding with IKKgamma, and the sensitivity of these vFLIP-expressing cells was examined by MTT assay with various anticancer drugs. The results indicated that vFLIP expression induced selective sensitization to bleomycin and another bleomycin-related reagents peplomycin. Regarding bleomycin sensitivity, bleomycin hydrolase inactivates bleomycin and decreases sensitivity to it. Interestingly, we found that vFLIP expression disturbed subcellular localization of bleomycin hydrolase although bleomycin hydrolase expression level was not affected. These observations suggest for the first time that an activation of IKK-pathway is a novel modulator of bleomycin chemosensitivity. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B71. |
| Databáze: | OpenAIRE |
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