title: Effect of Bcl-2 on apoptosis and transcription factor NF-κB activation induced by adriamycin in bladder carcinoma BIU87 cells.
abstract: Resistance to apoptosis is a major obstacle preventing effective therapy for malignancies. Bcl-2 plays a significant role in inhibiting apoptosis. We reconstructed a stable human Bcl-2 transfected cell line, BIU87- Bcl-2, that was derived from the transfection of human bladder carcinoma cell line BIU87 with a plasmid vector containing recombinant Bcl-2 [pcDNA3.1(+)-Bcl-2]. A cell line transfected with the plasmid alone [pcDNA3.1(+)- neo] was also established as a control. BIU87 and BIU87-neo proved sensitive to adriamycin induced apoptosis, while BIU87-Bcl-2 was more resistant. In view of the growing evidence that NF-κB may play an important role in regulating apoptosis, we determined whether Bcl-2 could modulate the activity of NF-κB in bladder carcinoma cells. Stimulation of BIU87, BIU87-neo and BIU87-Bcl-2 with ADR resulted in an increase expression of NF-κB (p<0.001). The expression of NF-κB in BIU87-Bcl-2 was higher than in the other two cases, with a concomitant reduction in the IκBκ?protein level. These results suggest that the overexpression of Bcl-2 renders human bladder carcinoma cells resistant to adriamycin -induced cytotoxicity and there is a link between Bcl-2 and the NF-κB signaling pathway in the suppression of apoptosis.
authors.affiliation: Department of Hematology, Shengjing Hospital of China Medical University, Shenyang, China. zhanggj@sj-hospital.org
authors.forename: Guo-Jun
authors.initials: GJ
authors.lastname: Zhang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects*; D004317:Doxorubicin / Q000494:pharmacology*; D005434:Flow Cytometry; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*
chemical_list: D000903:Antibiotics, Antineoplastic; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D004317:Doxorubicin