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★

The effective parts of total biflavones from selaginella inhibit diffuse large B-cell lymphoma by down-regulating PI3K/AKT pathway★

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 blotting验证TBF有效部位影响的信号通路。结果 TBF有效部位对DLBCL不同亚型细胞株的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。TBF有效部位主要对细胞内PI3K/AKT信号通路产生影响。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信号通路激活发挥抗DLBCL作用，为DLBCL临床治疗提供了新策略。

Abstract:

Objective To explore the effects and mechanism of total biflavonoids (TBF) effective parts extracted from Selaginella tamariscina on diffuse large B-cell lymphoma (DLBCL).Methods CCK-8 method was used to detect the effects of TBF effective parts on the proliferation of DLBCL cells. Flow cytometry was applied to detect the apoptosis and cell cycle of cells after treated by TBF effective parts. Transcriptome sequencing and enrichment of differential genes were conducted to preliminarily explore the mechanism of TBF effective parts in anti-DLBCL. Western blotting was used to verify the signaling pathways affected by TBF effective parts.Results The TBF effective parts significantly inhibited the proliferation of different types of DLBCL cell lines, induced an increase in the proportion of apoptosis of DLBCL cells, and blocked the cell cycle in G₂ phase. The TBF effective parts 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 TBF effective parts played an anti-DLBCL role by inhibiting the activation of the PI3K/AKT signaling pathway. TBF effective parts may serve as a new option for the treatment of DLBCL.