Cancer letters
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Although photodynamic therapy (PDT) has been approved by regulatory agencies worldwide for the treatment of several oncologic and non-oncologic conditions, PDT-induced tissue hypoxia as a result of vascular damage and photochemical oxygen consumption limits the efficacy of this modality. This may largely be due to hypoxia-mediated angiogenesis via hypoxia-inducible factor-1alpha (HIF-1alpha), a major transcription factor involved in angiogenesis, hematopoiesis and anaerobic energy metabolism. We hypothesized that hypoxia-induced HIF-1alpha overexpression may also lead to tumor cells resistant to PDT by favouring tumor cell proliferation. ⋯ We thus conclude that high-expression of HIF-1alpha induced by CoCl(2) plays an important role in the resistance of the Het-1A cells to ALA-PDT. The present finding suggests that hypoxia-induced HIF-1alpha overexpression attenuates PDT efficacy through probably not only angiogenesis, but also cellular resistance to the modality. PDT in combination with anti-HIF-1alpha treatment may thus enhance the PDT efficacy.