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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 | Clinical significance of autoantibodies to soluble liver antigen in autoimmune hepatitis 显示文摘 | Weidemann C Gerken G | 1999 | J Hepatol1999，31，： | 1 |
| 3 | Turnover rate and kinetic mechanism for the reaction of hydrodechlorination of 1, 1-dichlorotertrafluoroethane(CF3-CFCl2) over a polycrystalling Pd foil显示文摘 | Riberio F H Gerken C A Somorjai G A | 1997 | Catal Lett1997，45，： | 1 |
| 4 | Clinical significance of autoantibodies to soluble liver aneigen in autoimmue hepatitis显示文摘 | Kanzler S Weidemann C Gerken G | 1999 | J Hepatol1999，31，4： | 1 |
| 5 | The obesity-associated FTO gene encodes a 2-oxoglutar- ate-dependent nucleic acid demethylase显示文摘 | GERKEN T GIRARD C A TUNG Y C | 2007 | Science2007，318，5855： | 1 |
| 6 | SJES14110700138146显示文摘 | Michael Manns Stanislas Pol Ira M Jacobson Patrick Marcellin Stuart C Gordon Cheng-Yuan Peng Ting-Tsung Chang Gregory T Everson Jeong Heo Guido Gerken Boris Yoffe William J Towner Marc Bourliere Sophie Metivier Chi-Jen Chu William Sievert Jean-Pierre Bron | 2014 | The Lancet2014，，9954： | 1 |
| 7 | The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase显示文摘 | GERKEN T GITARD C A TUNG Y C | 2007 | Science2007，318，： | 1 |
| 8 | The obesity-associated FTO gene encodes a 2-oxoglutar-ate-dependent nucleic acid demethylase 显示文摘 | GERKEN T GIRARD C A TUNG Y C L | 2007 | Science2007，318，5855： | 1 |
| 9 | Expression and function of beta - glucuronidase in pancreatic cancer: potential role in drug targeting 显示文摘 | Sperker B Werner U Miirdter TE Tekkaya C Fritz P Wacke R Adam U Gerken M Drewelow B Kroemer HK | 2000 | Naunyn Schmiedebergs Arch Pharma- col2000，362，2： | 1 |
| 10 | Electrochemical water oxidation with cobalt-based electrocatalysts from pH 0-14:The thermodynamic basis for catalyst structure,stability,and activity显示文摘 | Gerken J B McAlpin J G Chen J Y C | | 0，，36： | 1 |
| 11 | The o-besity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase 显示文摘 | GERKEN T GIRARD C A TUNG Y L | 2007 | Science2007，318，5855： | 1 |
| 12 | Clinical significance of autoantibodies to soluble liver antigen in autoimmune hepatitis显示文摘 | Kanzler S Weidemann C Gerken G | 1999 | J Hep-atol1999，31，4： | 1 |
| 13 | The obesity-associated FTO gene encodes a 2-oxogLutarate-dependent nucLeic acid demethyLase显示文摘 | Gerken T Girard C A Tung Y C | 2007 | Science2007，318，： | 1 |
| 14 | Hepatitis B and liver transplantation: 2008 update 显示文摘 | Beckebaum S Sotiropoulos G C Gerken G | 2009 | Rev Med Virol2009，19，1： | 1 |
| 15 | The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase显示文摘 | Gerken T Girard C A Tung Y C L | 2007 | Science2007，318，5855： | 1 |
| 16 | Steroid-free, tacrolimus-basiliximab immunosuppression in pediatric liver transplantation: clinical and pharmacoeconomic study in 50 children显示文摘 | Gras JM Gerkens S Beguin C | 2008 | Liver Transpl2008，14，4： | 1 |
| 17 | The obesity -asso- ciated FrO gene encodes a 2 - oxoglutarate - dependent nucleic acid demethylase显示文摘 | GERKEN T GIRARD C A TUNG Y C | 2007 | Science2007，318，5855： | 1 |
| 18 | The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase 显示文摘 | GERKEN T GIRARD C A TUNG Y C | 2007 | Science2007，318，5855： | 1 |
| 19 | The obesityasso- ciated FTO gene encodes a 2 oxogluta rate dependent nucleic acid demethylase 显示文摘 | Gerken T Girard C A Tung Y C | 2007 | Science2007，8，5855： | 1 |
| 20 | Turnover rate and kinetic mechanism for the reaction of hydrodechlorination of 1,1-dichlorotetrafluoroethane ( CF3 -CFC12 ) over a polycrystalline Pd foil 显示文摘 | Ribeiro F H Gerken C A Somorjai G A | 1997 | Catal Lett1997，45，34： | 1 |
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