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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 | Fractionation of a light crude oil and identification and quantitation of aliphatic,aromatic,and biomarker compounds by GC-FID and GC-MS,Part II显示文摘 | Wang Z D Fingas M F Li K | 1994 | Journal of Chromatographic Science1994，32，9： | 1 |
| 3 | Development of oil hydrocarbon fingerprinting and techniques显示文摘 | Wang Z Fingas M F | 2003 | Marine Pollution Bulletin2003，，47： | 1 |
| 4 | Development of airborne oil thickness measurements 显示文摘 | Brown C E Fingas M F | 2003 | Marine Pollution Bulletin2003，47，9101112： | 1 |
| 5 | Modeling evaporation using models that are not boundary-layer regulated显示文摘 | Fingas M F | 2004 | Journal of Hazardous Materials2004，107，： | 1 |
| 6 | Developments in the analysis of petroleum hydrocarbons in oils,petroleum products and oil-spill-related environmental samples by gas chromatography显示文摘 | Wang Z Fingas M | 1997 | Journal of Chromatography A1997，，774： | 1 |
| 7 | Forensic fingerprinting ofbiomarkers for oil spill characterization and source identification显示文摘 | Wang Z Stout S A Fingas M | 2006 | Environmental Forensics2006，7，2： | 1 |
| 8 | A review of the status of advancedtechnologies for the detection of oil in and with ice显示文摘 | Merv Fingas Carl Brown | 2000 | SpillScience&Technology Bulletin2000，6，56： | 1 |
| 9 | Accelerated solvent extraction (ASE) of environmental organic compounds in soils using a modified supercritical fluid extractor显示文摘 | Li M Landriault M Fingas M | 2003 | Journal of Hazardous Materials2003，102，1： | 1 |
| 10 | Incidence and prevalence of spinal cord injury in Canada:a national perspective显示文摘 | Noonan VK Fingas M Farry A | | 0，，4： | 1 |
| 11 | Characterization and identification of the Detroit River mystery oil spill (2002)显示文摘 | Wang Z Fingas M Lambert P | 2004 | Journal of Chromatography A2004，1038，1： | 1 |
| 12 | The influence of hy-pothermia on outcome after intracerebral hemorrhage in rats显示文摘 | MacLellan C L Davies L M Fingas M S | 2006 | Stroke2006，37，5： | 1 |
| 13 | Effectiveness testing of oil spill-treating agents显示文摘 | Fingas M F Stoodley R Laroche N | 1990 | Marine Environmental Research1990，7，4： | 1 |
| 14 | Oil spill identification显示文摘 | Wang Z D Fingas M Page D S | 1999 | Journal of Chromatography A1999，843，12： | 1 |
| 15 | Comparison of oil composition changes due to biodegradation and physical weathering in different oils 显示文摘 | Wang Z D Fingas M Blenjinsopp S | 1998 | Journal of Chromatography A1998，809，： | 1 |
| 16 | Study of 22-year-old Arrow oil samples using biomarker compounds by GC/MS显示文摘 | Wang Z Fingas M Sergy G | 1994 | Environmental Science & Technology1994，28，9： | 1 |
| 17 | Fractionation of a light crude oil and identification and quantitation of aliphatic, aro- matic,and biomarker compounds by GC-FID and GC MS显示文摘 | WANG Zhendi FINGAS M F LI Ken | 1994 | Journal of Chromatographic Science1994，32，9： | 1 |
| 18 | Study of the 25-year-old Nipisi oil spill:persistence of oil residues and comparisonsbetween surface and subsurface sediments显示文摘 | Wang Z Fingas M Blenkinsopp S | 1998 | EnvironmentalScience&Technology1998，32，15： | 1 |
| 19 | Effect of temperature on the anaerobic thermophilic conversion of volatile fatty acids by dispersed and granular sludge 显示文摘 | LIER van J B MARTIN J L S LET'FINGA G | 1996 | Water Research1996，30，： | 1 |
| 20 | Rapid Generation of microRNA sponges for microRNA inhibition显示文摘 | KLUIVER J GIBCUS J H HET'FINGA C | 2012 | PLoS One2012，7，29： | 1 |
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