| http://purl.uniprot.org/citations/21843371 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/21843371 | http://www.w3.org/2000/01/rdf-schema#comment | "Gemcitabine is used to treat several cancers including lung cancer. However, tumor cells often escape gemcitabine-induced cell death via various mechanisms, which include modulating bcl-2 family members and NF-κB activation. We previously reported that the C-terminal region of Bfl-1 fused with GFP (BC) is sufficient to induce apoptosis in 293T cells. In the present study, we investigated the anti-tumor effect of combined BC gene therapy and gemcitabine chemotherapy in vitro and in vivo using non-small cell lung cancer cell lines and a xenograft model. Cell lines were resistant to low dose gemcitabine (4-40 ng/ml), which induced NF-κB activation and concomitant up-regulation of Bfl-1 (an NF-κB-regulated anti-apoptotic protein). BC induced the apoptosis of A549 and H157 cells with caspase-3 activation. Furthermore, co-treatment with BC and low dose gemcitabine synergistically and efficiently induced mitochondria-mediated apoptosis in these cells. When administered alone or with low dose gemcitabine, BC suppressed NF-κB activity, inhibited the nuclear translocation of p65/relA, and down-regulated Bfl-1 expression. Furthermore, direct suppression of Bfl-1 by RNA interference sensitized cells to gemcitabine-induced cell death, suggesting that Bfl-1 importantly regulates lung cancer cell sensitivity to gemcitabine. BC and gemcitabine co-treatment also showed a strong anti-tumor effect in a nude mouse/A549 xenograft model. These results suggest that lung cancer cells become resistant to gemcitabine via NF-κB activation and the subsequent overexpression of Bfl-1, and that BC, which has both pro-apoptotic and NF-κB inhibitory effects, could be harnessed as a gene therapy to complement gemcitabine chemotherapy in non-small cell lung cancer."xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.org/dc/terms/identifier | "doi:10.1186/1476-4598-10-98"xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/author | "Kim Y.H."xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/author | "Choi Y."xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/author | "Kim C.W."xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/author | "Kim M.K."xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/author | "Choi D.H."xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/author | "Woo J.K."xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/author | "Jeon Y.K."xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/date | "2011"xsd:gYear |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/name | "Mol Cancer"xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/pages | "98"xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/title | "The C-terminal region of Bfl-1 sensitizes non-small cell lung cancer to gemcitabine-induced apoptosis by suppressing NF-kappaB activity and down-regulating Bfl-1."xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://purl.uniprot.org/core/volume | "10"xsd:string |
| http://purl.uniprot.org/citations/21843371 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/21843371 |
| http://purl.uniprot.org/citations/21843371 | http://xmlns.com/foaf/0.1/primaryTopicOf | https://pubmed.ncbi.nlm.nih.gov/21843371 |
| http://purl.uniprot.org/uniprot/#_Q16548-mappedCitation-21843371 | http://www.w3.org/1999/02/22-rdf-syntax-ns#object | http://purl.uniprot.org/citations/21843371 |
| http://purl.uniprot.org/uniprot/Q16548 | http://purl.uniprot.org/core/mappedCitation | http://purl.uniprot.org/citations/21843371 |