卷柏总双黄酮有效部位通过抑制PI3K/AKT通路抗弥漫大B细胞淋巴瘤

卷柏总双黄酮有效部位通过抑制PI3K/AKT通路抗弥漫大B细胞淋巴瘤
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作者单位:中南大学
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基金项目:基金名称：湖南省中医药管理局一般项目，项目编号：D2022074，课题名称：卷柏中黄酮类成分对弥漫大B细胞淋巴瘤的抗肿瘤作用及机制研究。 基金名称：湖南省卫生健康委一般项目，项目编号：202203045455，课题名称：TBL1XR1高表达促进弥漫大B细胞淋巴瘤发生发展及作用机制。 基金名称：湖南省自然科学基金，项目编号：2022JJ30026，课题名称：FTO介导m6A修饰ATXN1L促进弥漫大B细胞淋巴瘤发生发展的研究。 基金名称：湖南省自然科学基金，项目编号：2022JJ30789，课题名称：HDAC抑制剂HS270下调MYBL2促进弥漫大B细胞淋巴瘤细胞衰老的机制。 基金名称：中南大学中央高校基础研究基金，项目编号：2023ZZTS0867，课题名称：卷柏中新双黄酮单体 FLA-14抗弥漫大B细胞淋巴瘤的作用及机制。 基金名称：中南大学中央高校基础研究基金，项目编号：2024ZZTS0918，课题名称：TBL1XR1促进弥漫大B细胞淋巴瘤发生发展的分子机制及临床转化研究。 基金名称：湖南省卫健委技术厅资助项目，项目编号：WZ2020-13，课题名称：淋巴瘤患者规范化诊疗技术。基金名称：长沙血液病精准诊疗技术创新中心，项目编号：[2024]NO.196

The Effective Parts of Total Biflavones from selaginella pulvinata inhibit Diffuse Large B-cell Lymphoma by Down-regulating PI3K/AKT Pathway

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摘要:

目的：探究卷柏总双黄酮（TBF）有效部位治疗弥漫大B细胞淋巴瘤(DLBCL)的作用及可能机制。方法：采用CCK-8法检测TBF有效部位对DLBCL细胞增殖的影响；流式细胞术检测TBF有效部位对DLBCL细胞凋亡及周期的影响；转录组学测序并富集差异基因初步探讨TBF有效部位抗DLBCL的作用机制；Western blot验证TBF有效部位影响的信号通路。结果：TBF有效部位对不同亚型的DLBCL细胞株增殖均有显著抑制作用，且可诱导DLBCL细胞凋亡，将细胞周期阻滞于G2期。对转录组测序的差异基因进行富集分析，TBF有效部位主要对细胞内PI3K-AKT信号通路产生影响，Western blot检测显示随着TBF有效部位浓度的增加，PI3K、AKT的表达量及p-PI3K、p-AKT与对照组相比显著降低。结论：TBF有效部位可通过抑制PI3K/AKT信号通路的激活发挥抗DLBCL作用，为DLBCL的临床治疗提供了新策略。

Abstract:

Objective: To explore the effects and mechanism of the effective parts of total biflavones (TBF) from selaginella pulvinata on diffuse large B-cell lymphoma (DLBCL). Methods: CCK-8 method was used to detect the effect of the effect parts of TBF on the proliferation of DLBCL cells. The apoptosis and cell cycle of cells were detected by flow cytometry. The mechanism of the effect parts of TBF in DLBCL was analyzed by transcriptome sequencing. Western blot was used to verify the results of transcriptome sequencing. Results: The effective parts of TBF significantly inhibited the proliferation of various types of DLBCL cell lines and could induce an increase in the proportion of apoptosis of DLBCL cells and block the cell cycle in G2 phase. By analyzing the differential genes obtained by transcriptome sequencing, the effect parts of TBF mainly affected the intracellular PI3K-AKT signaling pathway. Compared with the control group, the expression of PI3K and AKT, as well as their phosphorylated forms (p-PI3K and p-AKT), were significantly decreased in a TBF effective parts concentration dependent manner. Conclusion: The effective parts of TBF from selaginella pulvinata can inhibit DLBCL by down-regulating the activation of the PI3K/AKT signaling pathway, and the effective parts of TBF may serve as a new option for the treatment of DLBCL.