首页|桃红四物汤通过PI3K/AKT/HIF-1α通路介导的糖酵解抑制骨肉瘤的增殖与迁移

桃红四物汤通过PI3K/AKT/HIF-1α通路介导的糖酵解抑制骨肉瘤的增殖与迁移

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目的:探讨桃红四物汤(THSWD)是否通过磷脂酰肌醇3-激酶(PI3K)/蛋白激酶B(AKT)/缺氧诱导因子-1α(HIF-1α)通路介导的糖酵解抑制骨肉瘤(OS)增殖迁移.方法:制备THSWD含药血清.用不同浓度的含药血清培养人OS MG63与143B细胞.CCK-8实验、克隆实验、划痕愈合实验、Transwell实验观察不同剂量THSWD对OS细胞增殖、迁移的作用;通过Western Blot检测不同剂量THSWD含药血清对OS细胞的哺乳动物雷帕霉素靶蛋白(mTOR)、磷酸化mTOR(p-mTOR)、HIF-1α、PI3K、己糖激酶2(HK2)、AKT、磷酸化AKT(p-AKT)、葡萄糖转运体1(GluT1)的蛋白表达影响;试剂盒检测不同剂量THSWD含药血清对OS细胞胞内及上清液葡萄糖及乳酸含量的影响.结果:与空白组和对照组比较,不同剂量的THSWD均可以抑制OS细胞MG63与143B的增殖、克隆、迁移与侵袭(P<0.05);Western Blot检测显示,THSWD呈剂量依赖性抑制OS细胞MG63与143B中PI3K、p-AKT、GluT1蛋白表达(P<0.05);进一步研究结果显示,THSWD降低OS细胞内葡萄糖浓度(P<0.05),增加上清液葡萄糖浓度(P<0.05),但上清液和细胞内乳酸生成均减少(P<0.05).结论:THSWD抑制OS的增殖与迁移可能通过PI3K/AKT/HIF-1 α通路介导的糖酵解来实现,本研究为OS的临床治疗提供更多思路.
Inhibition of osteosarcoma proliferation and migration of Taohong Siwu Decoction via PI3K/AKT/HIF-1α pathway mediated glycolysis
Objective:To investigate whether Taohong Siwu Decoction(THSWD)is activated through phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/hypoxia inducible factor-1 α(HIF-1 α)pathway mediated glycolysis inhibits osteosarcoma(OS)proliferation and migration.Methods:THSWD medicated serum was prepared.Human OS MG63 and 143B cells were cultured with different concentrations of medicated serum.CCK-8 assay,cloning assay,scratch healing assay,Transwell assay were performed to observe the effects of different doses of THSWD on osteosarcoma cell proliferation and migration.The protein expressions of mammalian target of rapamycin(mTOR),phosphorylated mTOR(p-mTOR),HIF-1α,PI3K,hexokinase 2(HK2),AKT,phosphorylated AKT(p-AKT),glucose transporter 1(GluT1)were affected in osteosarcoma cells treated with different doses of THSWD containing serum were determined by Western Blot.The effects of different doses of THSWD containing serum on the intracellular and supernatant glucose and lactate contents of OS cells were detected using kits.Results:Compared with the blank group and the control group,different doses of THSWD could inhibit the proliferation,migration and invasion of OS MG63 and 143B cells(P<0.05);Western Blot assay showed that THSWD dose dependently inhibited the protein expression of PI3K,p-AKT,GluT1 in OS cells(P<0.05).Further study results showed that THSWD decreased the intracellular glucose concentration(P<0.05)and increased the supernatant glucose concentration(P<0.05),but decreased both the supernatant and intracellular lactate production(P<0.05).Conclusion:THSWD inhibits OS proliferation and migration possibly through PI3K/AKT/HIF-1 α pathway mediated glycolysis to achieve,this study provides more ideas for the clinical treatment of OS.

Taohong Siwu DecoctionPI3K/AKT/HIF-1 α pathwayGlycolysisOsteosarcoma(OS)MechanismGlucoseLactate

温蕊嘉、董鑫、麦泳欣、周舒婷、王俊岩、张锦芳

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广州中医药大学第一临床医学院,广州 510405

广州中医药大学深圳医院(福田),深圳 518000

广州中医药大学第一附属医院,广州 510405

广州中医药大学中药学院,广州 510006

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桃红四物汤 磷脂酰肌醇3-激酶/蛋白激酶B/缺氧诱导因子-1α通路 糖酵解 骨肉瘤 机制 葡萄糖 乳酸

国家自然科学基金面上项目

82272526

2024

中华中医药杂志
中华中医药学会

中华中医药杂志

CSTPCD北大核心
影响因子:1.135
ISSN:1673-1727
年,卷(期):2024.39(7)
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