Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0050786
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dc.titleCombination Therapy with Gossypol Reveals Synergism against Gemcitabine Resistance in Cancer Cells with High BCL-2 Expression
dc.contributor.authorWong, F.Y.
dc.contributor.authorLiem, N.
dc.contributor.authorXie, C.
dc.contributor.authorYan, F.L.
dc.contributor.authorWong, W.C.
dc.contributor.authorWang, L.
dc.contributor.authorYong, W.-P.
dc.date.accessioned2014-12-12T07:59:38Z
dc.date.available2014-12-12T07:59:38Z
dc.date.issued2012-12-04
dc.identifier.citationWong, F.Y., Liem, N., Xie, C., Yan, F.L., Wong, W.C., Wang, L., Yong, W.-P. (2012-12-04). Combination Therapy with Gossypol Reveals Synergism against Gemcitabine Resistance in Cancer Cells with High BCL-2 Expression. PLoS ONE 7 (12) : -. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0050786
dc.identifier.issn19326203
dc.identifier.urihttp://scholarbank.nus.edu.sg/handle/10635/116954
dc.description.abstractAlthough gemcitabine is highly active in several cancer types, intrinsic and acquired drug resistance remains a major challenge. Overexpression of Bcl-2 has been associated with gemcitabine resistance. The aim of this study is to determine whether gossypol can overcome gemcitabine resistance in cell lines with high level of Bcl-2 expression in combination drug therapy. Our study demonstrated that in 10 cell lines derived from different cancers, high Bcl-2 baseline expression was observed in cell lines that were resistant to gemcitabine (GEM-R). Furthermore, synergistic effect of combination therapy was observed in gemcitabine-resistant (GEM-R) cell lines with high Bcl-2 expression, but not in a gemcitabine-sensitive (GEM-S) cell lines regardless of Bcl-2 expression. Gossypol treatment resulted in the decrease of anti-apoptotic genes such as Bcl-2 and Bcl-xl and an upregulation of the pro-apoptotic gene, Noxa. Furthermore, the addition of gossypol to gemcitabine resulted in lower expressions of anti-apoptotic genes compared to gemcitabine alone. Gene expression profiling in GEM-R and GEM-S cell lines suggest that anti-apoptotic genes such as pAkt and PI3KR2 may play important role in gemcitabine resistance, while pro-apoptotic Bcl-2 related genes (Bad, Caspase-6 and Calpain-1) may regulate synergistic interaction in combination therapy. © 2012 Wong et al.
dc.description.urihttp://libproxy1.nus.edu.sg/login?url=http://dx.doi.org/10.1371/journal.pone.0050786
dc.sourceScopus
dc.typeArticle
dc.contributor.departmentCANCER SCIENCE INSTITUTE OF SINGAPORE
dc.description.doi10.1371/journal.pone.0050786
dc.description.sourcetitlePLoS ONE
dc.description.volume7
dc.description.issue12
dc.description.page-
dc.identifier.isiut000312108500031
dc.published.statePublished
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