Curcumin Inhibits Human Gastric Cancer Growth in Xenograft Murine Model through Downregulation of HIF-1α/MMP-9 Pathway
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Graphical Abstract
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Abstract
Objective To study the mechanism of curcumin inhibition of transplanted tumor growth in gastric cancer xenograft nude mice. Methods BGC-823 cells were treated with curcumin at concentration of 0,1,5, 10,20,50 mg/L for 24 h or 48 h,cells proliferation ability was detected by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cells invasion ability was detected by transwell assay.Gastric cancer xenograft nude mice model was established to assess the effect of curcumin inhibition on the xenografts.Additionally,Western blot was used to assess HIF-1α and MMP-9 protein expression levels in the xenografts.Luciferase assay was used to assessed the MMP-9 regulation by HIF-1α,and HIF-1α regulation by curcumin. Results Curcumin inhibited the proliferation of BGC-823 cells,and the effects were dose dependent in vivo and in vitro.The cells invasion ability was significantly reduced.HIF-1α and MMP-9 proteins expression were decreased.Curcumin inhibited HIF-1αand MMP-9 promoter activities on transcriptional level. Conclusion Curcumin inhibited human gastric cancer growth in vivo and in vitro through targeting HIF-1α/MMP-9 pathway transcription suppression,thereby inhibiting tumor invasion,as an anti-tumor effect.
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