کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2124589 | 1547233 | 2009 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Effect of HIF-1 modulation on the response of two- and three-dimensional cultures of human colon cancer cells to 5-fluorouracil
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Tumour hypoxia represents a major obstacle to the success of radiotherapy and chemotherapy. The discovery that the hypoxia-inducible factor 1 (HIF-1) is a master regulator of cellular response to low oxygen led to the concept that inhibiting HIF-1 activity may sensitise hypoxic cancer cells to radiation and cytotoxic drugs. In the present study we investigate the effects of HIF-1 modulation on the response of the human colon adenocarcinoma cell line HCT116 to 5-fluorouracil (5FU). Increasing HIF-1 activity, either by exposing cells to hypoxia or by forced expression of a degradation-resistant form of HIF-1α, results in poor cell response to 5FU; conversely, knockdown of HIF-1α by RNA interference prevents hypoxia-induced resistance to 5FU. PMX290, a thioredoxin-1 inhibitor, significantly inhibits HIF-1 activity and concomitantly sensitises hypoxic cells to 5FU. These results were confirmed in HCT116 cells grown as three-dimensional spheroids, a model that more closely reproduces the hypoxic environment of solid tumours.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Cancer - Volume 45, Issue 5, March 2009, Pages 890-898
Journal: European Journal of Cancer - Volume 45, Issue 5, March 2009, Pages 890-898
نویسندگان
Raffaella Ravizza, Roberta Molteni, Marzia B. Gariboldi, Emanuela Marras, Gianpaolo Perletti, Elena Monti,