中国实验血液学杂志2024,Vol.32Issue(5) :1438-1443.DOI:10.19746/j.cnki.issn1009-2137.2024.05.021

化瘀解毒汤抑制多发性骨髓瘤恶性生物学特性的作用机制

Mechanism of Huayu Jiedu Decoction in Inhibiting Malignant Biological Characteristics of Multiple Myeloma

李祚涛 李海亮 严志民 林洁 陈小芸 刘彦权 王钇力
中国实验血液学杂志2024,Vol.32Issue(5) :1438-1443.DOI:10.19746/j.cnki.issn1009-2137.2024.05.021

化瘀解毒汤抑制多发性骨髓瘤恶性生物学特性的作用机制

Mechanism of Huayu Jiedu Decoction in Inhibiting Malignant Biological Characteristics of Multiple Myeloma

李祚涛 1李海亮 2严志民 2林洁 1陈小芸 2刘彦权 3王钇力4
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作者信息

  • 1. 赣南医科大学第一附属医院重症医学科,江西赣州 341000
  • 2. 赣南医科大学第一附属医院血液内科,江西赣州 341000
  • 3. 广东医科大学附属东莞第一医院血液内科,广东东莞 523808
  • 4. 赣南医科大学第一附属医院肿瘤科,江西赣州 341000
  • 折叠

摘要

目的:探讨化瘀解毒汤对多发性骨髓瘤(MM)细胞恶性生物学特性的影响及其分子机制,为抗MM的中医替代治疗提供实验基础与理论依据.方法:采用不同浓度化瘀解毒汤干预骨髓瘤U266细胞,CCK-8法检测细胞增殖活性改变情况,Annexin V/PI双染流式细胞术检测凋亡情况,Western blot检测凋亡及相关信号通路蛋白表达变化,实时荧光定量PCR技术检测高迁移率族蛋白B1(HMGB1)、CXC趋化因子受体4(CXCR4)以及白细胞介素-6(IL-6)mRNA的表达变化.结果:化瘀解毒汤可抑制U266细胞的增殖活性,并诱导其发生凋亡,呈浓度及时间依赖性(r=-0.713,r=-0.827).化瘀解毒汤干预U266细胞48 h后,可下调抗凋亡蛋白Bcl-2、survivin的表达,并上调促凋亡蛋白Bax的表达,同时抑制TLR4/NF-κB信号通路的磷酸化水平.化瘀解毒汤干预U266细胞后,可显著降低HMGB1、IL-6 mRNA的表达,但对CXCR4 mRNA的表达基本无影响.结论:化瘀解毒汤能抑制U266细胞增殖活性并诱发程序性死亡,其分子机制可能与调控各凋亡蛋白表达以及抑制TLR4/NF-κB通路激活并下调HMGB1、IL-6 mRNA的表达有关.

Abstract

Objective:To analyze and explore the effects of Huayu Jiedu Decoction on the malignant biological characteristics of multiple myeloma(MM)cells and its molecular mechanism,so as to provide experimental basis and theoretical basis for the alternative therapy of anti-MM in traditional Chinese medicine.Methods:Different concentrations of Huayu Jiedu Decoction were used to intervene myeloma U266 cells.The changes of cell proliferation activity were detected by CCK-8 assay,apoptosis was detected by Annexin V/PI double staining flow cytometry,and apoptosis and protein expression of related signaling pathways were detected by Western blot.Real-time quantitative PCR was used to detect mRNA expression changes of high mobility group protein B1(HMGB1),CXC chemokine receptor 4(CXCR4)and interleukin-6(IL-6).Results:Huayu Jiedu Decoction inhibited the proliferative activity of U266 cells and induced their apoptosis in a concentration and time dependent manner(r=-0.713,r=-0.827).After treatment with Huayu Jiedu Decoction for 48 h,the expressions of anti-apoptotic protein Bcl-2 and survivin were down-regulated,while the expression of pro-apoptotic protein Bax was up-regulated,and the phosphorylation level of TLR4/NF-κB signaling pathway was inhibited.After intervention of Huayu Jiedu decoction,the expressions of HMGB1 and IL-6 mRNA were significantly decreased,while the expression of CXCR4 was not significantly decreased.Conclusion:Huayu Jiedu Decoction can inhibit the proliferative activity of U266 cells and induce programmed death.Its molecular mechanism may be related to regulating the expression of apoptotic proteins,inhibiting the activation of TLR4/NF-κB pathway and down-regulating the expression of HMGB1 and IL-6 mRNA.

关键词

化瘀解毒汤/多发性骨髓瘤/恶性生物学特性/抗癌机制

Key words

Huayu Jiedu decoction/multiple myeloma/malignant biological characteristics/anticancer mechanism

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出版年

2024
中国实验血液学杂志
中国病理生理学会

中国实验血液学杂志

CSTPCDCSCD北大核心
影响因子:0.988
ISSN:1009-2137
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