虎杖苷对AML细胞增殖、迁移、侵袭及肿瘤生长的影响
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篇名: 虎杖苷对AML细胞增殖、迁移、侵袭及肿瘤生长的影响
TITLE: Effects of polydatin on the cell proliferation,migration,invasion and tumor growth of AML
摘要: 目的 探讨虎杖苷(PD)对急性髓系白血病(AML)细胞增殖、迁移、侵袭及肿瘤生长的影响。方法将人AML细胞KG-1分为正常组,低、中、高浓度PD组(10、30、60μmol/L的PD),SQ22536组[环磷酸腺苷(cAMP)抑制剂,100μmol/L],高浓度PD和SQ22536联用组(60μmol/L的PD+100μmol/L的SQ22536),考察PD对细胞活力、凋亡率、侵袭和迁移能力、cAMP水平和上皮-间充质转化(EMT)相关蛋白、蛋白激酶A(PKA)蛋白表达的影响。以BALB/c裸鼠为对象,通过皮下接种KG-1细胞悬液建立AML裸鼠移植瘤模型,并分为对照组、PD组、SQ22536组、PD+SQ22536组(每组6只),考察PD对其瘤体体积及质量的影响。结果与正常组细胞或对照组裸鼠比较,PD各浓度组的细胞活力、迁移细胞数、侵袭细胞数和波形蛋白、锌指转录因子Snail蛋白的相对表达量,以及PD组裸鼠的瘤体体积及质量均显著降低,而细胞凋亡率、cAMP水平、PKA和上皮钙黏素的相对表达量均显著升高,且呈浓度依赖性(P<0.05);SQ22536对细胞和裸鼠的作用效果与PD相反,并可显著逆转PD的抗肿瘤活性(P<0.05)。结论PD可能通过激活cAMP/PKA信号通路来抑制AML细胞的增殖、迁移、侵袭,诱导细胞凋亡,抑制EMT进程及肿瘤生长,从而发挥抗AML作用。
ABSTRACT: OBJECTIVE To investigate the effects of polydatin (PD) on cell proliferation, migration, invasion and tumor growth of acute myeloid leukemia (AML). METHODS Human AML cell KG-1 were divided into normal group, PD low-, medium- and high-concentration groups (10, 30, 60 μmol/L PD), SQ22536 group [cyclic adenosine monophosphate (cAMP) inhibitor, 100 μmol/L], high concentration of PD+SQ22536 group (60 μmol/L PD+100 μmol/L SQ22536). The effects of PD on cell activity, apoptotic rate, invasion and migration ability, cAMP level, the expression of epithelial-mesenchymal transition (EMT) related proteins and protein kinase A (PKA) were investigated. Using BALB/c nude mice as subjects, a transplanted tumor model of AML nude mice was induced by subcutaneous inoculation of KG-1 cell suspension and then divided into control group, PD group, SQ22536 group and PD+SQ22536 group (with 6 mice in each group). The effects of PD on tumor volume and mass were measured. RESULTS Compared with the normal group or control group, the cell viabilities, the number of migrating cells, the number of invasive cells, the relative expressions of vimentin and Snail as well as the tumor volume and mass were decreased significantly in PD groups, while the apoptotic rates, cAMP levels, the relative expressions of E-cadherin and PKA were significantly increased, with a dose-dependent manner (P<0.05). SQ22536 had opposite effects on cells and nude mice compared to PD, and could significantly reverse the anti-tumor activity of PD (P<0.05). CONCLUSIONS PD may inhibit the proliferation, migration, invasion and EMT process of KG-1 cells, induce apoptosis, and inhibit tumor growth, by activating the cAMP/PKA signaling pathway, thereby exerting anti-AML effects.
期刊: 2024年第35卷第06期
作者: 华敏;张伟丽
AUTHORS: HUA Min,ZHANG Weili
关键字: 虎杖苷;急性髓系白血病;增殖;迁移;侵袭;上皮-间充质转化;环磷酸腺苷/蛋白激酶A信号通路
KEYWORDS: polydatin; acute myeloid leukemia; proliferation; migration; invasion; epithelial-mesenchymal transition; cAMP/
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