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 G(0)/G(1) 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.
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:Humancolorectal 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 G(0)/G(1) 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.
Authors: Young Min Chung; Wen Bin Tsai; Pragya P Khan; Jessica Ma; Jonathan S Berek; James W Larrick; Mickey C-T Hu Journal: Am J Cancer Res Date: 2022-03-15 Impact factor: 6.166
Authors: Thomas Thomaidis; Annett Maderer; Andrea Formentini; Susanne Bauer; Mario Trautmann; Michael Schwarz; Wiebke Neumann; Jens Martin Kittner; Arno Schad; Karl-Heinrich Link; Johannes Wilhelm Rey; Arndt Weinmann; Arthur Hoffman; Peter Robert Galle; Marko Kornmann; Markus Moehler Journal: J Exp Clin Cancer Res Date: 2014-10-02
Authors: Enikő Tátrai; Alexandra Bartal; Alexandra Gacs; Sándor Paku; István Kenessey; Tamás Garay; Balázs Hegedűs; Eszter Molnár; Mihály T Cserepes; Zita Hegedűs; Nóra Kucsma; Gergely Szakács; József Tóvári Journal: Oncotarget Date: 2017-07-04