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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 | Pollution performance of DC insulators under operating conditions显示文摘 | Changetal T C Steffens H G Marks J | 1981 | IEEE Trans on EI1981，16，3： | 2 |
| 3 | Role of oxidants and antioxidants in atherosclerosis: results of in vitro and in vivo investigations显示文摘 | SIEKMEIER R STEFFEN C MERZ W | 2007 | Journal of Cardiovascular Pharmacology and Therapeutics2007，12，4： | 1 |
| 4 | Polyacrylic fibers显示文摘 | Gries T Rixe C Steffens M | 2002 | Chemical Fibers International2002，52，： | 1 |
| 5 | A new flux splitting scheme 显示文摘 | LIOU Meng-sing Steffen C J | 1993 | Journal of Computational Physics1993，107，1： | 1 |
| 6 | Statins reduce interleukin-6-induced Creactive protein in human hepatocytes: new evidence for direct anti inflammatory effects of statins 显示文摘 | Arnaud C Burger F Steffens S | 2005 | Arterioscler Thromb Vasc Biol2005，25，6： | 1 |
| 7 | A New Flux 显示文摘 | Liou M S Steffen Splitting Scheme C J | 1993 | Journal of Computational Physics1993，107，1： | 1 |
| 8 | The molecular pathogenesis of acute myeloid leukemia 显示文摘 | STEFFEN B MULLER - TIDOW C SCHWABLE J | 2005 | Crit Rev Oncol Hematol2005，56，： | 1 |
| 9 | Mineralization of 14 C-labelled synthetic lignin and extracellular enzyme activities of the wood-colonizing ascomycetes Xylaria hy-poxylon and Xylaria polymorpha显示文摘 | Liers C Ullrich R Steffen K T | | 0，，05： | 1 |
| 10 | Overexpression of polyphenol oxidase in transgenic tomato plants results in enhanced bacterial disease resistance显示文摘 | Li L Steffens J C | 2002 | Planta2002，215，2： | 1 |
| 11 | Multidetector computedtomography for preoperative assessment of hepatic vasculatureand prediction of splenic artery steal syndrome in patients withliver cirrhosis before transplantation显示文摘 | Grieser C Denecke T Steffen IG | 2010 | Eur Radiol2010，20，1： | 1 |
| 12 | Fredenc woringer,Pautrier-Woringer disease(lipomelanotic reticulosis/dermatopathic lymphadenitis)显示文摘 | Steffen C | 2004 | Am J Dermatopathol2004，26，6： | 1 |
| 13 | In vitro effects of 2- methoxyestradiol on MCF-12A and MCF-7 cell growth,morpholo- gy and mitotic spindle formation 显示文摘 | Van Zijl C Lottering M L Steffens F | 2008 | Cell Biochem Funct2008，26，63： | 1 |
| 14 | Incorporation ofpodoplanin into HIV releasedfrom HEK-293T cells, butnot PBMC,is required forefficient binding to theattachment factor CLEC-2显示文摘 | Chaipan C Steffen I Tsegaye TS | 2010 | Retrovirology2010，2010，： | 1 |
| 15 | 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 |
| 16 | Polyacrylic fibers 显示文摘 | Gries T Rixe C Steffens M | 2002 | Chem Fibers Int2002，52，4： | 1 |
| 17 | Selection and characterization of HER2/neu-binding affibody ligands显示文摘 | Wikman M Steffen A C Gunneriusson E | 2004 | Protein Eng Des Sel2004，17，5： | 1 |
| 18 | Prevalence of depression among older Americans: the aging, demographics and memory, study 显示文摘 | STEFFENS D C FISHER G G LANGA K M | 2009 | Int Psychogeriatr2009，21，5： | 1 |
| 19 | CD44 expression and regulation during mammary gland development and function显示文摘 | Hebbard L Steffen A Zawadzki V Fieber C | 2000 | J Cell Sci2000，113，： | 1 |
| 20 | A new flux splitting scheme显示文摘 | Liou M S Steffen C J | 1993 | Journal of Computational Physics1993，107，： | 1 |
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