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The c-kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy

(2002) CANCER RESEARCH. 62(17). p.4879-4883
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Abstract
The c-kit tyrosine kinase inhibitor STI571 exhibits a substantial therapeutic activity in patients with chronic myeloid leukemia and gastrointestinal stromal tumors respectively associated with constitutive activation of the BCR-ABL and c-kit tyrosine kinases. Human colorectal tumors also express the c-kit proto-oncogene. The present study focuses on the anticancer activity of STI571 in human colorectal tumor cells in vitro and in vivo. The c-kit receptor was identified as a M-r 145,000 immunoreactive band in human colon cancer cells HT29, HCT8/S11, and HCT116. Cellular invasion induced by 10 ng/ml stem cell factor (EC50 = 3 ng/ml) in HT29 cells was blocked by 1 mum STI571 (IC50 = 56 nM) and pharmacological inhibitors of several oncogenic signaling pathways, namely, phosphatidylinositol 3-kinase (LY294002), Rho GTPases (Clostridium botulinum exoenzyme C3 transferase), and Rho-kinase (Y27632). STI571 inhibited HT29 cell proliferation (IC50 = 6 muM) and induced apoptosis in vitro. These cellular effects were associated with a decrease in tumor growth. We also demonstrated that stem cell factor is a proangiogenic factor in vivo and in vitro. These encouraging results warrant further preclinical investigations and clinical trials on the use of the e-kit inhibitor STI571 as a chemotherapeutic agent in colon cancer prevention and in treatment of advanced colorectal cancers associated with liver metastases.
Keywords
INDUCED APOPTOSIS, CELLULAR INVASION, RANDOMIZED TRIAL, HEMATOPOIETIC-CELLS, PHILADELPHIA-CHROMOSOME, FIRST-LINE TREATMENT, FIBROBLAST-GROWTH-FACTOR, COLONIC EPITHELIAL-CELLS, DEPENDENT SIGNALING PATHWAYS, GASTROINTESTINAL STROMAL TUMORS

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Citation

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Chicago
Attoub, Samir, Christine Rivat, Sylvie Rodrigues, Saskia Van Bocxlaer, Monique Bedin, Erik Bruyneel, Christophe Louvet, et al. 2002. “The C-kit Tyrosine Kinase Inhibitor STI571 for Colorectal Cancer Therapy.” Cancer Research 62 (17): 4879–4883.
APA
Attoub, S., Rivat, C., Rodrigues, S., Van Bocxlaer, S., Bedin, M., Bruyneel, E., Louvet, C., et al. (2002). The c-kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy. CANCER RESEARCH, 62(17), 4879–4883.
Vancouver
1.
Attoub S, Rivat C, Rodrigues S, Van Bocxlaer S, Bedin M, Bruyneel E, et al. The c-kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy. CANCER RESEARCH. 2002;62(17):4879–83.
MLA
Attoub, Samir, Christine Rivat, Sylvie Rodrigues, et al. “The C-kit Tyrosine Kinase Inhibitor STI571 for Colorectal Cancer Therapy.” CANCER RESEARCH 62.17 (2002): 4879–4883. Print.
@article{151820,
  abstract     = {The c-kit tyrosine kinase inhibitor STI571 exhibits a substantial therapeutic activity in patients with chronic myeloid leukemia and gastrointestinal stromal tumors respectively associated with constitutive activation of the BCR-ABL and c-kit tyrosine kinases. Human colorectal tumors also express the c-kit proto-oncogene. The present study focuses on the anticancer activity of STI571 in human colorectal tumor cells in vitro and in vivo. The c-kit receptor was identified as a M-r 145,000 immunoreactive band in human colon cancer cells HT29, HCT8/S11, and HCT116. Cellular invasion induced by 10 ng/ml stem cell factor (EC50 = 3 ng/ml) in HT29 cells was blocked by 1 mum STI571 (IC50 = 56 nM) and pharmacological inhibitors of several oncogenic signaling pathways, namely, phosphatidylinositol 3-kinase (LY294002), Rho GTPases (Clostridium botulinum exoenzyme C3 transferase), and Rho-kinase (Y27632). STI571 inhibited HT29 cell proliferation (IC50 = 6 muM) and induced apoptosis in vitro. These cellular effects were associated with a decrease in tumor growth. We also demonstrated that stem cell factor is a proangiogenic factor in vivo and in vitro. These encouraging results warrant further preclinical investigations and clinical trials on the use of the e-kit inhibitor STI571 as a chemotherapeutic agent in colon cancer prevention and in treatment of advanced colorectal cancers associated with liver metastases.},
  author       = {Attoub, Samir and Rivat, Christine and Rodrigues, Sylvie and Van Bocxlaer, Saskia and Bedin, Monique and Bruyneel, Erik and Louvet, Christophe and Kornprobst, Michel and André, Thierry and Mareel, Marcus and Mester, Jan and Gespach, Christian},
  issn         = {0008-5472},
  journal      = {CANCER RESEARCH},
  keywords     = {INDUCED APOPTOSIS,CELLULAR INVASION,RANDOMIZED TRIAL,HEMATOPOIETIC-CELLS,PHILADELPHIA-CHROMOSOME,FIRST-LINE TREATMENT,FIBROBLAST-GROWTH-FACTOR,COLONIC EPITHELIAL-CELLS,DEPENDENT SIGNALING PATHWAYS,GASTROINTESTINAL STROMAL TUMORS},
  language     = {eng},
  number       = {17},
  pages        = {4879--4883},
  title        = {The c-kit tyrosine kinase inhibitor STI571 for colorectal cancer therapy},
  url          = {http://cancerres.aacrjournals.org/content/62/17/4879},
  volume       = {62},
  year         = {2002},
}

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