کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1933964 1050630 2009 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Inhibitors of insulin-like growth factor-1 receptor tyrosine kinase are preferentially cytotoxic to nutrient-deprived pancreatic cancer cells
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Inhibitors of insulin-like growth factor-1 receptor tyrosine kinase are preferentially cytotoxic to nutrient-deprived pancreatic cancer cells
چکیده انگلیسی

Chronic deprivation of nutrients is rare in normal tissues, however large areas of tumor are nutrient-starved and hypoxic due to a disorganized vascular system. Some cancers show an inherent ability to tolerate severe growth conditions. Therefore, we screened chemical compounds to identify cytotoxic agents that function preferentially in nutrient-deprived conditions. We found that AG1024, a specific inhibitor of insulin-like growth factor-1 receptor tyrosine kinase (IGF-1R), showed preferential cytotoxicity to human pancreatic cancer cells in nutrient-deprived conditions relative to cells in nutrient-sufficient conditions. The cytotoxicity of I-OMe-AG538 (another specific inhibitor of IGF-1R kinase) was also enhanced in nutrient-deprived cells. In addition, AG1024 and I-OMe-AG538 potently inhibited IGF-1R activation to nutrient-deprived cells. In contrast, conventional chemotherapeutic drugs, as well as inhibitors of PDGFR and EGFR kinases, elicited weak cytotoxicity. These data indicate that nutrient-deprived human pancreatic cancer cells have increased sensitivity to inhibition of IGF-1R activation. IGF-1R inhibitors offer a promising strategy for anticancer therapeutic approaches that are oriented toward tumor microenvironment.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 380, Issue 1, 27 February 2009, Pages 171–176
نویسندگان
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