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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 | 显示文摘 | Vick Roy T B Blanch H W Wilke C R | 1983 | Trends of Biotecnology1983，1，： | 1 |
| 3 | Genetic Control of High Oleic Acid Content in Sunflower Oil 显示文摘 | Miller J F Zimmerman D C Vick B A | 1987 | Crop Science1987，27，5： | 1 |
| 4 | Sound detection of stored-product insects that feed inside kernels of grain 显示文摘 | VICK K M WEBB J C WEABER B A | 1988 | Journal of Economic Entomology1988，81，5： | 1 |
| 5 | Bildgebung bei neuroendokrinentumoren des Pankreas显示文摘 | Vick C Zech CJ H?pfner S | | 0，，04： | 1 |
| 6 | Thin film microstructure control using glancing angle deposition by sputtering 显示文摘 | J C Sit D Vick K Robbie | 1999 | Journal of Materials Research1999，14，4： | 1 |
| 7 | Cure of phenol-formaldehyde adhe- sive in the presence of CCA-treated wood by differential scanning calorimetry显示文摘 | Vick C B Christiansen A W | 1993 | Wood and Fiber Science1993，25，1： | 1 |
| 8 | Lipoxygenase in Chlorella pyrenoidosa显示文摘 | Zimmerman D C Vick B A | 1973 | Lipids1973，8，5： | 1 |
| 9 | Metabolism of fatty acid hydroperoxides by Chlorlla Pyrenalidosa 显示文摘 | Vick B A Zimmerman D C | 1989 | Plant Physiol1989，90，： | 1 |
| 10 | Lipoxygenase and hydroperoxide lyase in germinating watermelon seedlings 显示文摘 | Vick B A Zimmerman D C | 1976 | Plant Physiol1976，57，5： | 1 |
| 11 | Construction of an RFLP linkage map for cultivated sunflower 显示文摘 | Jan C C Vick B A Miller J F | 1998 | Theor Appl Genet1998，96，： | 1 |
| 12 | Acoustical monitoring of Rhyzopertha dominica ( Coleoptera : Bostrichidae ) populations in stored wheat显示文摘 | Hagstrum D W Vick K W Webb J C | 1990 | Journal of Economic Entomology1990，83，2： | 1 |
| 13 | Sound detection of stored-product insects that feed inside kernels of grain 显示文摘 | Vick K W Webb J C Weaver B A | 1988 | Journal of Economic En- tomology1988，81，5： | 1 |
| 14 | Choice of intravenous antibiotic prophylaxis for colorectal surgery does matter显示文摘 | Deierhoi RJ Dawes LG Vick C | 2013 | J Ameri College Surg2013，217，5： | 1 |
| 15 | computed tomography of benign ovarian masses显示文摘 | Sawyer RW Vick C Walsh JW | 1985 | J comout Assist Tomosr1985，9，4： | 1 |
| 16 | Genetic control of high oleic acid content in sunflower oil显示文摘 | MILLER J F ZIMMERMAN D C VICK B A | 1987 | Crop Science1987，27，5： | 1 |
| 17 | Developmint of a novolak-based hydroxymethylated resorcinol coupling agent for wood adhesives显示文摘 | Christiansen A W Vick C B Okkonen E A | 2003 | Forest Products Journal2003，53，2： | 1 |
| 18 | Characterization of a new Bacdlus thunngiensis isolate highly active a- gainst Cochylis hospes显示文摘 | Bai C Vick B A Yi S X | 2002 | Current Microbiology2002，44，： | 1 |
| 19 | Surgical site infection pre- vention:time to move beyond the surgical care improvement pro gram显示文摘 | Hawn M T Vick C C Richman J | 2011 | AnnSurg2011，254，3： | 1 |
| 20 | Acoustical monitoring of Rhyzopertha dominica populations in stored wheat 显示文摘 | Hagstrum D W Vick K W Webb J C | 1990 | Journal of Economic Entomology1990，83，： | 1 |
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