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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 | Meteorosensitive architecture: Biomimetic building skins based onmaterially embedded and hygroscopically enabled responsiveness显示文摘 | Steffen R Achim M David C | 2015 | Computer-Aided Design2015，60，： | 1 |
| 3 | Defective Interplay of Activators and Repressors with TFIIH in Xeroderma Pigmentosum显示文摘 | Juhong Liu Sasha Akoulitchev Achim Weber Hui Ge Sergei Chuikov Daniel Libutti Xin W Wang Joan Weliky Conaway Curtis C Harris Ronald C Conaway Danny Reinberg David Levens | 2001 | Cell2001，，3： | 1 |
| 4 | Polyphenol screening of pomace from red and white grape varieties (Vitis vinifera L.) by HPLC-DAD-MS/MS显示文摘 | Dietmar K Achim C Reinhold C | | 0，，： | 1 |
| 5 | Thermodynamics of bcc metals in phase-field-crystal models显示文摘 | Jaatinen A Achim C V Elder K R | | 0，，： | 1 |
| 6 | Impact of formulation and technological factors on the acrylamide content of wheat bread and bread rolls显示文摘 | Achim C Melanie M Georg W | 2008 | Journal of Cereal Science2008，47，54： | 1 |
| 7 | Neural transplantation for stroke显示文摘 | Kondziolka D Wechsler L Achim C | 2002 | J Clin Neurosci2002，9，3： | 1 |
| 8 | Neural transplantation for stroke 显示文摘 | Kondziolka D Wechsler L Achim C | 2002 | J Clin Neurosci2002，9，3： | 1 |
| 9 | Clinicopathologic study for the assessment of resection for ampullary carcinoma显示文摘 | Thomas C Botter JB Achim H | 1997 | World J Surg1997，22，4： | 1 |
| 10 | Neural Transplantation for stroke显示文摘 | Kondziolka D Wechsler L Achim C | 2002 | J Clin Neurosci2002，9，3： | 1 |
| 11 | Impact of formulation and technological factors on the acrylamide content of wheat bread and bread rolls显示文摘 | ACHIM C MELANIE M GEORG W | 2008 | J Cereal Sci2008，47，3： | 1 |
| 12 | Herpes simplex virus brainstem encephalitis in an AIDS patient显示文摘 | Hamilton R L Achim C Grafe M R | 1995 | Clin Neuropathol1995，14，1： | 1 |
| 13 | Use of ^137Cs to estimate tillage-and water-induced soil redistribution rates on agricultural land under different use and management in central-south Chile显示文摘 | Paulina S Achim E Alejandra C | 2003 | Soil and Tillage Research2003，69，： | 1 |
| 14 | Influence of ex- trinsic factors on electron transfer in a mixed-valence FeE*/Fe3 complex: experimental results and theoretical considerations 显示文摘 | Achim C Bominaar E L Staples R J | 2001 | lnorg Chem2001，40，17： | 1 |
| 15 | Expression of HIV regulatory and structural mRNA in the central nervous system 显示文摘 | Wiley C A Baldwin M Achim C L | 1996 | AIDS1996，10，8： | 1 |
| 16 | Modelling the vulnerability of balsam fir forests to wind damage显示文摘 | Achim A Ruel J C Gardiner B A | 2005 | Forest Ecology and Management2005，204，： | 1 |
| 17 | Impact of formulation and technological factors on the acrylamide content of wheat bread and bread rolls 显示文摘 | Achim C Melanie M Georg W | 2008 | Journal of Cereal Science2008，47，： | 1 |
| 18 | Tuberculosis, malnutrition and wasting 显示文摘 | Schwenk Achim Macallan Derek C | 2000 | Current Opinion in Clinical Nutrition & Metabolic Care2000，3，4： | 1 |
| 19 | Modeling the vulnerability of balsam fir forests to wind damage 显示文摘 | ACHIM A RUEL J C GARDINER B A | 2005 | ForEcol Manage2005，204，： | 1 |
| 20 | Clinicopathologic study for the assessment of resection for ampullay carcinoma显示文摘 | Thomas C Botter JB Achim H | 1997 | Warld J Surg1997，22，4： | 1 |
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