Hypoxia Induced Multidrug Resistance of Laryngeal Cancer Cells via Hypoxia-inducible Factor-1α

Objectives: To investigate whether hypoxia has an effect on regulation of multidrug resistance (MDR) tochemotherapeutic drugs in laryngeal carcinoma cells and explore the role of hypoxia-inducible factor-1α (HIF-1α).
Methods: Laryngeal cancer cells were cultured under normoxic and hypoxic conditions. The sensitivityof the cells to multiple drugs and levels of apoptosis induced by paclitaxel were determined by MTT assay andannexin-V/propidium iodide staining analysis, respectively. HIF-1α expression was blocked by RNA interference.The expression of HIF-1α gene was detected by real-time quantitative RT-PCR and Western blotting. The valueof fluorescence intensity of intracellular adriamycin accumulation and retention in cells was evaluated by flowcytometry.
Results: The sensitivity to multiple chemotherapy agents and induction of apoptosis by paclitaxelcould be reduced by hypoxia (P<0.05). A the same time, the adriamycin releasing index of cells was increased(P<0.05). However, resistance acquisition subject to hypoxia in vitro was suppressed by down-regulating HIF-1αexpression.
Conclusion: HIF-1α could be considered as a key regulator for mediating hypoxia-induced MDR inlaryngeal cancer cells via inhibition of drug-induced apoptosis and decrease in intracellular drug accumulation.