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| 1 | Bcl-2 degradation is an additional pro-apoptotic effect of polo-like kinase inhibition in cholangiocarcinoma cells显示文摘AIM To examine the influence on apoptotic mechanisms following inhibition of polo-like kinases as therapeuticallyapproach for cholangiocellular cancer treatment. METHODS As most cholangiocarcinomas are chemotherapyresistant due to mechanisms preventing tumor cell death, we investigated the effect of Cisplatin on cholangiocellular carcinoma(CCA) cell lines KMCH-1 and Mz-Ch-1. Polo-like kinases(PLK) are important regulators of the cell cycle and their inhibition is discussed as a potential therapy while PLK inhibition can regulate apoptotic mediators. Here, cells were treated with PLK inhibitor BI6727(Volasertib), Cisplatin, and in combination of both compounds. Cell viability was assessed by MTT; apoptosis was measured by DAPI staining and caspase-3/-7 assay. Western blot and q RT-PCR were used to measure expression levels of apoptosis-related molecules Bax and Bcl-2. RESULTS The cell viability in the CCA cell lines KMCH-1 and Mz-Ch-1 was reduced in all treatment conditions compared to vehicle-treated cells. Co-treatment with BI6727 and cisplatin could even enhance the cytotoxic effect of cisplatin single treatment. Thus, co-treatment of cisplatin with BI6727 could slightly enhance the cytotoxic effect of the cisplatin in both cell lines whereas there was evidence of increased apoptosis induction solely in Mz-Ch-1 as compared to KMCH-1. Moreover, PLK inhibition decreases protein levels of Bcl-2; an effect that can be reversed by the proteasomal degradation inhibitor MG-132. In contrast, protein levels of Bax were not found to be altered by PLK inhibition. These findings indicate that cytotoxic effects of Cisplatin in Mz-Ch-1 cells can be enhanced by co-treatment with BI6727.CONCLUSION In conclusion, BI6727 treatment can sensitize CCA cells to cisplatin-induced apoptosis with proteasomal Bcl-2 degradation as an additional pro-apoptotic effect. | Svenja Sydor Sami Jafoui Lena Wingerter Sandra Swoboda Joachim C Mertens Guido Gerken Ali Canbay Andreas Paul Christian D Fingas | 2017 | World Journal of Gastroenterology2017，23，22： | 5 |
| 2 | Endothelial cell activation by endotoxin involves superoxide/NO-mediated nitration of prostacyclin synthase and thromboxane receptor stimulation 显示文摘 | Markus Bachschmid Svenja Thurau Zou Ming-hui | 2003 | FASEB J2003，17，8： | 1 |
| 3 | Microfabricated alkali atom vapor cells显示文摘 | Li Anne Liew Svenja Knappe John Moreland | 2004 | Application Physical Letter2004，84，14： | 1 |
| 4 | Assessing tillage disturbance on assemblages of ground beetles (Coleoptera: Carabidae) by using a range of ecological indices显示文摘 | Svenja Belaoussoff Peter G. Kevan Stephen Murphy Clarence Swanton | 2003 | Biodiversity and Conservation2003，，5： | 1 |
| 5 | Ulva, Umbraulva and Gemina: genetic survey of New Zealand taxa reveals diversity and introduced species 显示文摘 | SVENJA H JUDY E S B KATE F N | 2009 | European Journal of Phycology2009，44，2： | 1 |
| 6 | Enteric Bacteria Counteract Lipopolysaccharide Induction of Antimicrobial Peptide Genes显示文摘 | Lindmark H Iohansson K C Svenja S | 2001 | Immun2001，167，： | 1 |
| 7 | Laser Noise Cancellation in Single-Cell CPT Clocks显示文摘 | Vladislav Gerginov Svenja Knappe Vishal Shah | 2008 | IEEE Transactions on Instrumentation and Measurement2008，57，7： | 1 |
| 8 | Epithelial tight junctions in intestinal in ammation 显示文摘 | Joerg S Svenja P Maren A | 2009 | New York Academy of Sciences2009，116，5： | 1 |
| 9 | Inducible and repressable oncogene-addicted hepatocellular carcinoma in Tet-on xmrk transgenic zebrafish显示文摘 | Zhen Li Xiaoqian Huang Huiqing Zhan Zhiqiang Zeng Caixia Li Jan M. Spitsbergen Svenja Meierjohann Manfred Schartl Zhiyuan Gong | 2011 | Journal of Hepatology2011，，2： | 1 |
| 10 | Fucoidansand fucoidanases-focus on techniques for molecularstructure elucidation and modification of marinepolysaccharides显示文摘 | Andrea D H Svenja K Roland U | 2009 | Appl Microbiol Biotechnol2009，82，1： | 1 |
| 11 | Failure mechanisms of magnesia alumina spinel abradable coatings under thermal cyclic loading显示文摘 | Svenja Ebert Robert Mücke Daniel Mack Robert Va?en Detlev St?ver Tanja Wobst Susanne Gebhard | 2013 | Journal of the European Ceramic Society2013，，： | 1 |
| 12 | Managing Complexity and Unforeseeable Uncertainty in Startup Companies: An Empirical Study显示文摘 | Svenja C. Sommer Christoph H. Loch Jing Dong | 2009 | Organization Science2009，，1： | 1 |
| 13 | Assessing tillage disturbance on assemblages of ground beetles (Coleoptera: Carabidae) by using a range of ecological indices显示文摘 | Svenja Belaoussoff Peter G. Kevan Stephen Murphy Clarence Swanton | | 0，2003，： | 1 |
| 14 | 《口语语料库语言学:从单模态到多模态》介绍显示文摘《口语语料库语言学:从单模态到多模态》(Spoken Corpus Linguistics. FromMonomodal to Multimodal)由英国诺丁汉大学SvenjaAdolphs和RonaldCarter两位教授合著,2013年4月由Routledge出版。该书为“Routledge语料库语言学新进展”系列丛书的第15种。除引言外,该书分为两大部分,共8章。下面逐一介绍主要内容。 | Svenja Adolphs Ronald Carter 方清明 | 2017 | 当代语言学2017，19，1： | 1 |
| 15 | In vitro stimulation with HBV therapeutic vaccine candidate Nasvac activates B and T cells from chronic hepatitis B patients and healthy donors显示文摘 | Yadira Lobaina Svenja Hardtke Heiner Wedemeyer Julio Cesar Aguilar Verena Schlaphoff | 2014 | Molecular Immunology2014，，： | 1 |
| 16 | The effect of coal particle size on pyrolysis and steam gasification显示文摘 | Patrick J W Walker A Hanson Svenja | 2002 | Fuel2002，81，5： | 1 |
| 17 | Genetic identification of forensically important flesh flies (Diptera: Sarcophagidae)显示文摘 | Richard Zehner Jens Amendt Svenja Schütt Jan Sauer Roman Krettek Dalibor Povolny | 2004 | International Journal of Legal Medicine2004，，4： | 1 |
| 18 | Fueoidans an(/fueoidanas- es-focus on techniques for molecular structure elucidation and modification of marine polysaccharides显示文摘 | Andrea D H Svenja K Roland U | 2009 | Applied Microbiology and Bioteehnology2009，82，1： | 1 |
| 19 | Hypoxia can induce c-Met expression in glioma cells and enhance SF/HGFdnduced cell mi gration显示文摘 | Carmen N Svenja Z Regina F | 2007 | Cancer2007，121，2： | 1 |
| 20 | Remifentanil Directly Activates Human N-methyl-d-aspartate Receptors Expressed in Xenopus laevis Oocytes显示文摘 | Klaus Hahnenkamp Joke Nollet Hugo K. Van Aken Hartmut Buerkle Tobias Halene Svenja Schauerte Anke Hahnenkamp Markus W. Hollmann Danja Strümper Marcel E. Durieux Christian W. Hoenemann | 2004 | Anesthesiology2004，，6： | 1 |
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