| 付岳亚,李颖璐,赵耀,等.大豆黄素通过巨噬细胞移动抑制因子抑制肝癌细胞增殖[J].浙江中医药大学学报,2023,47(9):976-985. |
| 大豆黄素通过巨噬细胞移动抑制因子抑制肝癌细胞增殖 |
| Mechanism of Glycitein on Inhibiting the Proliferation of Hepatoma Cells by Macrophage Migration Inhibitory Factor |
| DOI：10.16466/j.issn1005-5509.2023.09.002 |
| 中文关键词: 大豆黄素 巨噬细胞移动抑制因子 肝癌细胞 抑制 增殖 凋亡 细胞周期 调控 |
| 英文关键词: Glycitein macrophage migration inhibitory factor hepatoma cell inhibition proliferation apoptosis cell cycle regulation |
| 基金项目:河南省医学科技攻关计划项目(201901335) |
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| 中文摘要: |
| [目的] 探讨大豆黄素(Glycitein)通过巨噬细胞移动抑制因子(migration inhibitory factor，MIF)抑制肝癌细胞增殖的机制。[方法] 采用生物信息学分析大豆黄素作用靶点，并分析该靶点在肝癌组织中表达及其与临床不良表型之间的关系。将肝癌细胞(HepG2和HepB3)分成正常组、Glycitein组(Glycitein处理)和Glycitein+MIF组(转染MIF并用Glycitein处理)。采用不同浓度Glycitein干预，以细胞增殖实验检测细胞活力；细胞克隆实验检测Glycitein对细胞生长能力的影响；细胞周期实验检测Glycitein对细胞周期的影响；细胞凋亡实验检测Glycitein对细胞凋亡的影响；裸鼠移植瘤实验检测Glycitein体内抑制细胞增殖；免疫组化检测增殖细胞抗原Ki67；免疫印迹法检测细胞MIF以及凋亡相关蛋白表达。[结果] MIF是Glycitein作用靶点，在肝癌组织中高表达，且与肝癌临床不良表型有关。Glycitein作用后，能够抑制肝癌细胞增殖和细胞周期进程，并诱导细胞凋亡。裸鼠移植瘤实验显示，Glycitein作用裸鼠后，明显抑制移植瘤体积和质量增长。Glycitein组细胞Ki67相对表达量明显低于正常组(P<0.05)。Glycitein能够呈浓度和时间依赖性地抑制肝癌细胞MIF蛋白表达。与Glycitein+MIF-NC组比较，Glycitein+MIF组细胞增殖、克隆增高，而G0/G1期细胞比例减低，凋亡细胞数量减少(P<0.05)。与Glycitein+MIF-NC组比较，Glycitein+MIF组细胞B细胞淋巴瘤/白血病-2(B cell lymphoma/leukemia-2，Bcl-2)、细胞周期蛋白依赖性激酶2(cyclin-dependent kinases 2，CDK2)、细胞周期蛋白B1(cyclin B1，CCNB1)和Ki67蛋白表达增高(P<0.05)，Bcl-2相关X蛋白(Bcl-2 related X，Bax)蛋白表达减低(P<0.05)。[结论] Glycitein通过靶向调控MIF蛋白表达，抑制肝癌细胞增殖，阻滞细胞周期，促进细胞凋亡。 |
| 英文摘要: |
| [Objective] To explore the mechanism of Glycitein on inhibiting the proliferation of hepatoma cells by targeting macrophage migration inhibitory factor(MIF). [Methods] The target of Glycitein was analyzed by bioinformatics， and expression of the target in hepatoma tissues and its relationship with adverse clinical phenotypes were analyzed. In the experiment， hepatoma cells(HepG2， HepB3) were divided into normal group， Glycitein group(Glycitein treatment) and Glycitein+MIF group(MIF transfection and Glycitein treatment). The cells were treated with different concentrations of Glycitein， the cells activity was detected by cells proliferation assay， the effects of Glycitein on cells growth were detected by cells clone assay， the effects of Glycitein on cells growth cycle were detected by cell cycle assay， the effects of Glycitein on apoptosis were detected by apoptosis assay. The inhibition of cells proliferation in vivo by Glycitein was detected by xenograft tumor assay of nude mice. The proliferating cell antigen Ki67 was detected by immunohistochemistry. MIF and expressions of apoptosis-related proteins were detected by Western blot. [Results] MIF was the target of Glycitein， which was highly expressed in hepatoma tissues and related to adverse clinical phenotypes of hepatoma. Glycitein could inhibit cells proliferation and cycle process， and induce apoptosis. The xenograft tumor assay of nude mice showed that Glycitein could significantly inhibit volume and mass growth of xenograft tumors. The relative expression level of Ki67 in Glycitein group was significantly lower than that in normal group(P<0.05). Glycitein could inhibit the expression of MIF in hepatoma cells， showing concentration and time dependence. Compared with Glycitein +MIF-NC group，the number of proliferation and clone were increased in Glycitein+MIF group， while proportion of G0/G1 stage cells and the number of apoptosis cells were decreased(P<0.05). Compared with Glycitein+MIF-NC group， the expressions of B cell lymphoma/leukemia-2(Bcl-2)， cyclin-dependent kinases 2(CDK2)， cyclin B1(CCNB1) and Ki67 were increased(P<0.05)， while the expression of Bcl-2 related X(Bax) was decreased in Glycitein+MIF group(P<0.05). [Conclusion] Glycitein can inhibit the proliferation of hepatoma cells， block cells cycle and promote apoptosis by targeting MIF. |
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