RT Journal Article
SR Electronic
T1 SN-38 Overcomes Chemoresistance of Colorectal Cancer Cells Induced by Hypoxia, through HIF1alpha
JF Anticancer Research
JO Anticancer Res
FD International Institute of Anticancer Research
SP 865
OP 872
VO 32
IS 3
A1 KOJI MURONO
A1 NELSON H. TSUNO
A1 KAZUSHIGE KAWAI
A1 KAZUHITO SASAKI
A1 KUMIKO HONGO
A1 MANABU KANEKO
A1 MASAYA HIYOSHI
A1 NORIKO TADA
A1 TAKAKO NIREI
A1 EIJI SUNAMI
A1 KOKI TAKAHASHI
A1 JOJI KITAYAMA
YR 2012
UL http://ar.iiarjournals.org/content/32/3/865.abstract
AB Background: Cancer cells can acquire resistance to therapy under hypoxic condition. We aimed to investigate the mechanisms regulating chemoresistance induced by hypoxia. Materials and Methods: Human colorectal cancer cells, HT-29 and SW480, were cultured under hypoxic conditions and the sensitivity to 5-fluorouracil (FU), oxaliplatin, and SN-38 (active metabolite of irinotecan) was tested. The cell cycle was evaluated by flow cytometry after staining of cells with propidium iodide (PI). hypoxia-inducible factor 1α (HIF-1α) expression was evaluated by western blot analysis. Results: Hypoxia induced strong G0/G1 cell cycle arrest of cancer cells and abrogated the cytotoxic effects of 5-FU and oxaliplatin, but not that of SN-38. This effect was dependent on the significant inhibition of the accumulation of HIF-1α in cancer cells cultured under hypoxia by SN-38. Neither 5-FU nor oxaliplatin affected HIF-1α expression. Conclusion: SN-38, through inhibition of HIF-1α can overcome chemoresistance under hypoxic conditions of colon cancer cells.