The C-terminal region of Bfl-1 sensitizes non-small cell lung cancer to gemcitabine-induced apoptosis by suppressing NF-kappa B activity and down-regulating Bfl-1
DC Field | Value | Language |
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dc.contributor.author | Kim, Min-Kyoung | - |
dc.contributor.author | Jeon, Yoon-Kyung | - |
dc.contributor.author | Woo, Jong-Kyu | - |
dc.contributor.author | Choi, Yun | - |
dc.contributor.author | Choi, Dae-Han | - |
dc.contributor.author | Kim, Yeul-Hong | - |
dc.contributor.author | Kim, Chul-Woo | - |
dc.date.accessioned | 2021-09-07T09:20:19Z | - |
dc.date.available | 2021-09-07T09:20:19Z | - |
dc.date.created | 2021-06-19 | - |
dc.date.issued | 2011-08-16 | - |
dc.identifier.issn | 1476-4598 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/111782 | - |
dc.description.abstract | 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-kappa B 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-kappa B activation and concomitant up-regulation of Bfl-1 (an NF-kappa B-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-kappa B 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-kappa B activation and the subsequent overexpression of Bfl-1, and that BC, which has both pro-apoptotic and NF-kappa B inhibitory effects, could be harnessed as a gene therapy to complement gemcitabine chemotherapy in non-small cell lung cancer. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | BIOMED CENTRAL LTD | - |
dc.subject | PANCREATIC-CANCER | - |
dc.subject | DEOXYCYTIDINE KINASE | - |
dc.subject | POTENTIAL MECHANISM | - |
dc.subject | CASPASE ACTIVATION | - |
dc.subject | GENE-EXPRESSION | - |
dc.subject | UP-REGULATION | - |
dc.subject | RESISTANCE | - |
dc.subject | BCL-2 | - |
dc.subject | INHIBITION | - |
dc.subject | DEATH | - |
dc.title | The C-terminal region of Bfl-1 sensitizes non-small cell lung cancer to gemcitabine-induced apoptosis by suppressing NF-kappa B activity and down-regulating Bfl-1 | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Yeul-Hong | - |
dc.identifier.doi | 10.1186/1476-4598-10-98 | - |
dc.identifier.scopusid | 2-s2.0-80051626450 | - |
dc.identifier.wosid | 000294536100001 | - |
dc.identifier.bibliographicCitation | MOLECULAR CANCER, v.10 | - |
dc.relation.isPartOf | MOLECULAR CANCER | - |
dc.citation.title | MOLECULAR CANCER | - |
dc.citation.volume | 10 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Biochemistry & Molecular Biology | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalWebOfScienceCategory | Biochemistry & Molecular Biology | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.subject.keywordPlus | PANCREATIC-CANCER | - |
dc.subject.keywordPlus | DEOXYCYTIDINE KINASE | - |
dc.subject.keywordPlus | POTENTIAL MECHANISM | - |
dc.subject.keywordPlus | CASPASE ACTIVATION | - |
dc.subject.keywordPlus | GENE-EXPRESSION | - |
dc.subject.keywordPlus | UP-REGULATION | - |
dc.subject.keywordPlus | RESISTANCE | - |
dc.subject.keywordPlus | BCL-2 | - |
dc.subject.keywordPlus | INHIBITION | - |
dc.subject.keywordPlus | DEATH | - |
dc.subject.keywordAuthor | gemcitabine | - |
dc.subject.keywordAuthor | NF-kappa B | - |
dc.subject.keywordAuthor | Bfl-1 | - |
dc.subject.keywordAuthor | gene therapy | - |
dc.subject.keywordAuthor | non-small cell lung cancer | - |
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