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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 | Loss of gata1 but not gata2 converts erythropoiesis to myelopoiesis in zebrafish embryos显示文摘 | Galloway JL Wingert RA Thisse C | 2005 | Dev Cell2005，8，1： | 1 |
| 3 | The development of silver-based cadmium-free contact materials显示文摘 | Wingert P C Leung C H | 2004 | Journal of Alloys and Compounds2004，72，3： | 1 |
| 4 | Deficiency of glutaredoxin 5 reveals Fe-S clusters are required for vertebrate haem synthesis 显示文摘 | Wingert R A Galloway J L Barut B | 2005 | Nature2005，436，7053： | 1 |
| 5 | Cellular effects of catabolic inflammatory cytokines on chondrocytes-biomed 显示文摘 | Lawyer T Wingerter S Tucci M | 2011 | Biomed Sci Instrum2011，47，4： | 1 |
| 6 | x-Bond anisotropy and C - D??? Q hydrogen bonding in the crystal structure of deuterionitromethane显示文摘 | Jeffrey G A Ruble] R Wingert L M | 1985 | J Am Chern Soc1985，107，： | 1 |
| 7 | Synthese und Reaktivitat von Diphenyl phosphany Itrimethylsilylamin Ph2PN (H)SiMe 3 显示文摘 | WINGERTER S PFEIFFER M BAIER F STEY T STALKE D | 2000 | Z Anorg Allg Chem2000，626，： | 1 |
| 8 | Comparison of the inherent erosion behaviors of silver-cadmium oxide and silver-tin oxide contact materials显示文摘 | Leung C H | 1987 | IEEE Trans Comp1987，10，1： | 1 |
| 9 | The development of silver-based cadmi- um-free contact materials显示文摘 | Leung C H | 1989 | IEEE Trans Comp1989，12，1： | 1 |
| 10 | Hip disease and hip arthroplasty显示文摘 | Wingerter SA Mehrle RK | 2011 | Orthop Clin North Am2011，42，1： | 1 |
| 11 | The effects of graphite partieal size and processing on the performance of silver graphite eontaets显示文摘 | Wingert P C Allen S E Bevington R C | 1992 | IEEE CHMT1992，15，2： | 1 |
| 12 | A structural model for Duck hepatitis B virus core protein derived by extensive mutagenesis 显示文摘 | NASSAL M LEIFER I WINGERT I | 2007 | J Virol2007，81，13： | 1 |
| 13 | The zebrafish proneptuos : a model to study nephron segmentation显示文摘 | WINGERT R A DAVIDSON A J | 2008 | Kidney Int2008，73，： | 1 |
| 14 | New tides: using zebrafish to study renal regeneration显示文摘 | Kristen K. McCampbell Rebecca A. Wingert | 2013 | Translational Research2013，，： | 1 |
| 15 | GC-MS analysis of diamondoid hydrocarbons in Smackover petroleums显示文摘 | Wingert W S | 1992 | Fuel1992，71，1： | 1 |
| 16 | Zebrafish nephrogenesis is regulated by interactions between retinoic acid, mecom , and Notch signaling显示文摘 | Yue Li Christina N. Cheng Valerie A. Verdun Rebecca A. Wingert | 2013 | Developmental Biology2013，，： | 1 |
| 17 | The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephros 显示文摘 | WINGERT R A SELLECK R YU J | 2007 | PEoS Genet2007，3，： | 1 |
| 18 | What drives the development of USmissile defense and space-based weapons? The role of USdomestic interest groups显示文摘 | WINGERTER R | 2011 | Asian Perspective2011，35，： | 1 |
| 19 | Regenerative medicine for the kidney: stem cell prospects & challenges显示文摘 | Yue Li Rebecca A Wingert | 2013 | Clinical and Translational Medicine2013，，1： | 1 |
| 20 | Zebrafish pronephros tubulogenesis and epithelial identity maintenance are reliant on the polarity proteins Prkc iota and zeta显示文摘 | Gary F. Gerlach Rebecca A. Wingert | 2014 | Developmental Biology2014，，： | 1 |
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