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.