Gambogic Acid Promotes Hypoxia Nasopharyngeal Carcinoma Cell Radiation Sensitivity By Inducing G2/M Arrest

?Objectives? Hypoxia is an important factor that causes decreased local control as well as increased distant metastases and resistance to radiotherapy in advanced nasopharyngeal carcinoma(NPC)patients.Gambogic acid(GA),the major active ingredient of gamboge,possesses antitumor effect in vitro and in vivo.However,the potent molecular mechanism of whether GA inhibits tumor radioresistance remains unclear.The present study aimed to investigate the radiosensitizing effects of GA on NPC and explore the underlying mechanisms.?Materials and methods? CNE-1 and CNE-2 cells were exposed to hypoxia and radiation treated with Gambogic acid at different concentrations.The CCK-8 assay,clonogenic assay,and flow cytometry were performed to analyze cell proliferation,colony formation,apoptosis,and cell cycles.The expression of HIF-1a,Bcl-2,Bax,caspase-3,cyclin B1/p-cdc2 and ?-H2 AX were assessed using Western blot and/or immunofluorescence analysis.?Results? Results of cck8 assay,clonogenic assay,and flow cytometry showed that treatment of NPC cells with growth suppressive concentrations of GA resulted in G2/M phase arrest and apoptosis.Western blot analysis demonstrated that GA-induced cell cycle arrest and apoptosis in CNE-2 cells was associated with the upregulated expression of caspase-3 and Bax and the downregulation of Bcl2 and cyclin B1/p-cdc2 expression under hypoxia.Treatment with GA markedly decreased the expression of hypoxia-inducible factor-1?(HIF-1?)under hypoxic condition.?Conclusion? The present study indicated that GA efficiently radiosensitized NPC cells,implying the effect is probably associated with the down-regulation of HIF-1? and expression.