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Objective: Keloid is a benign tumor in the derma, which is generally treated by surgical excision and radiation in clinic. However, recurrence has been an intricate problem in treatment of keloid. Therefore, it is imperative to develop novel interfering means to increase the sensitivity of keloid to radiation. Quercetin is a natural compound, which has been shown to sensitize some tumors to radiation. We tested the potential of quercetin in sensitizing keloid fibroblast to radiation and identified its downstream pathways.
Methods: Keloid fibroblast cells were challenged by radiation with or without the presence of quercetin. Cellular response was detected by flow cytometry, western blot, qRT-PCR and immunofluorescence staining. HIF-1α was down-regulated by siRNA transfection.
Results: In this study, we firstly demonstrate that keloid fibroblasts acquire resistance after IR treatment, and this can be relieved by treating with quercetin. Further, we showed that hypoxia-inducible factor 1 (HIF-1), a prognostic marker used in clinical practice after radiation therapy, was associated with stronger radioresistance in keloid fibroblast, which was downregulated after quercetin treatment. The inhibition on HIF-1 expression by quercetin was found to depend on phosphatidylinositol-3-kinase (PI3K)/Akt pathway and quercetin also reduce phosphorylation of Akt.
Conclusion: Taken together, we revealed a mechanism underlying the suppression on radioresistance by quercetin, which involves the regulation of HIF-1α by PI3K/Akt pathway. Our study provides molecular interpretation for the application quercetin in sensitizing radiation in keloid treatment.