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| 1 | Bcl-x_L and Myeloid cell leukaemia-1 contribute to apoptosis resistance of colorectal cancer cells显示文摘AIM: To explore the role of Bcl-xL and Myeloid cell leukaemia (Mcl)-1 for the apoptosis resistance of colorectal carcinoma (CRC) cells towards current treat-ment modalities. METHODS: Bcl-xL and Mcl-1 mRNA and protein ex-pression were analyzed in CRC cell lines as well as human CRC tissue by Western blot,quantitative PCRand immunohistochemistry. Bcl-xL and Mcl-1 protein expression was knocked down or increased in CRC cell lines by applying specific siRNAs or expression plas-mids,respectively. After modulation of protein expres-sion,CRC cells were treated with chemotherapeutic agents,an antagonistic epidermal growth factor recep-tor (EGFR1) antibody,an EGFR1 tyrosine kinase inhibi-tor,or with the death receptor ligand TRAIL. Apoptosis induction and cell viability were analyzed. RESULTS: Here we show that in human CRC tis-sue and various CRC cell lines both Bcl-xL and Mcl-1 are expressed. Bcl-xL expression was higher in CRC tissue than in surrounding non-malignant tissue,both on protein and mRNA level. Mcl-1 mRNA expression was significantly lower in ma-lignant tissues. However,protein expression was slightly higher. Viability rates of CRC cells were significantly decreased after knock down of Bcl-xL expression,and,to a lower extent,after knock down of Mcl-1 expression. Furthermore,cells with reduced Bcl-xL or Mcl-1 expression was more sensitive towards oxaliplatin-and irinotecan-induced apoptosis,and in the case of Bcl-xL also towards 5-FU-induced apoptosis. On the other hand,upregulation of Bcl-xL by transfec-tion of an expression plasmid decreased chemothera-peutic drug-induced apoptosis. EGF treatment clearly induced Bcl-xL and Mcl-1 expression in CRC cells. Apop-tosis induction upon EGFR1 blockage by cetuximab or PD168393 was increased by inhibiting Mcl-1 and Bcl-xL expression. More strikingly,CD95-and TRAIL-induced apoptosis was increased by Bcl-xL knock down. CONCLUSION: Our data suggest that Bcl-xL and,to a lower extent,Mcl-1,are important anti-apoptotic factors in CRC. Specific downregulation of Bcl-xL is a promising approach to sensitize CRC cells towards chemotherapy and targeted therapy. | Henning Schulze-Bergkamen Roland Ehrenberg Lothar Hickmann Binje Vick Toni Urbanik Christoph C Schimanski Martin R Berger Arno Schad Achim Weber Steffen Heeger Peter R Galle Markus Moehler | 2008 | World Journal of Gastroenterology2008，14，24： | 4 |
| 2 | Analysis of PSLQ, an integer relation finding algorithm显示文摘 | Ferguson H R P Bailey D H Arno S | 1999 | Math Comput1999，68，225： | 1 |
| 3 | Robustness of device-independent dimension witnesses显示文摘 | Dali Arno M Passaro E Gallego R | 2012 | Physical Review A2012，86，04： | 1 |
| 4 | Synthesis of C-17-functionalized spongiane diterpenes: diastereoselective syn- thesis of (-)-spongian-16-oxo-17-al, (-)-acetyldendrillol-1 and (-)-aplyroseol--14显示文摘 | ARNO M GONZALEZ M A ZARAGOZA R J | 2003 | J Org Chem2003，68，： | 1 |
| 5 | High-dose saquinavir plus ritonavir: long-term efficacy in HIV-positive protease inhibitor-experienced patients and predictors of virologic response显示文摘 | Paredes R Puig T Arno A | 1999 | J AIDS1999，22，2： | 1 |
| 6 | Quantitative determination of cannabionoids from cannabis using ^1H-NMR 显示文摘 | Arno H K Choi Y H Verpoorte R | 2004 | Chem Pharm Bull2004，52，6： | 1 |
| 7 | Application of monitored natural attenuation in contaminated land management—A review and recommended approach for Europe显示文摘 | Hermann Rügner Michael Finkel Arno Kaschl Martin Bittens | 2006 | Environmental Science and Policy2006，，6： | 1 |
| 8 | Recent progress in the study of therheology of wood 显示文摘 | ARNO P SCHNIEWIND R | 1968 | Wood science and technology1968，2，： | 1 |
| 9 | Preparation and functionalization of multilayer fullerenes 显示文摘 | Arno S R Bevan E Joan S H | 2006 | Chem Eur J2006，12，2： | 1 |
| 10 | Spatial correlograms of soil cover as an indicator of landscape heterogeneity显示文摘 | Evelyn U Juri R Arno K Ulo M | 2008 | Eclogical Indicators2008，8，： | 1 |
| 11 | Preparation and Functionalization of Multilayer Fullerenes显示文摘 | Arno S R Bevan E Joan S H | 2006 | Chem Eur J2006，12，2： | 1 |
| 12 | KIR in type 1 diabetes disparate distribution of activating and inhibitory natural killer cell receptors in patients versus HLA-matched control subjects显示文摘 | Arno R van der Slik B Koeleman PC | 2003 | Diabetes2003，52，10： | 1 |
| 13 | Market competition: everybody is talking, but what do they say?: Asociological analysis of market competition in policy networks显示文摘 | Paulus A Arno V R Jan V M et ol | 2003 | Health Policy2003，64，： | 1 |
| 14 | Development of methods for the determination of pKa values 显示文摘 | Jetse R Arno van Hoof Antonie | 2013 | Anal Chem Insights2013，8，： | 1 |
| 15 | Does fairness prevent market clearing? An experimental investigation显示文摘 | Fehr E Georg K Arno R | 1993 | Quarterly Journal of Economics1993，76，3： | 1 |
| 16 | Preparation and functionalization of multilayer fullerenes (carbon nano-onions)显示文摘 | Arno S R Bevan E Joan S H | 2006 | Chem Eur J2006，12，2： | 1 |
| 17 | Production of D-amino acid oxidase(DAO) of Trigonopsis variabilis in Schizosaccharomyces pombe and the characterization of Biocatalysts prepared with Recombinant Cells 显示文摘 | Atsushi I Hidetoshi K Arno R | 2002 | Biotech Bioeng2002，80，： | 1 |
| 18 | Wavelet Transform Based Multifractal Formalism in Outlier Detection and Localization for Financial Time Series 显示文摘 | Zbigniew R Struzik Arno P J M Siebes | 2002 | Physica A: Statistical Mechanics and its Appli- cations2002，309，3： | 1 |
| 19 | Epilepsy in small-world networks显示文摘 | Netoff TI Clewley R Arno S | 2004 | J Neurosci2004，24，： | 1 |
| 20 | Wavelet Transform Based Multi - fractal Formalism in Outlier Detection and Localisation for Financial Ttime Sseries 显示文摘 | Zbigniew R Struzik Arno P J M Siebes | 2002 | Physica A3092002，，： | 1 |
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