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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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华 敏 ,张伟丽(滕州市中心人民医院输血科,山东 滕州 277599)
中图分类号 R965 文献标志码 A 文章编号 1001-0408(2024)06-0701-06
DOI 10.6039/j.issn.1001-0408.2024.06.11
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、60 μmol/L 的 PD),SQ22536 组[环磷酸腺苷(cAMP)抑制剂,100 μmol/L],高浓度 PD 和
SQ22536联用组(60 μmol/L的PD+100 μmol/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。
关键词 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
Effects of polydatin on the cell proliferation, migration, invasion and tumor growth of AML
HUA Min,ZHANG Weili(Dept. of Blood Transfusion, Tengzhou Central People’s Hospital, Shandong
Tengzhou 277599, China)
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.
KEYWORDS polydatin; acute myeloid leukemia; proliferation; migration; invasion; epithelial-mesenchymal transition; cAMP/
PKA signaling pathway
急性髓系白血病(acute myeloid leukemia,AML)是 织中髓系原始细胞克隆性扩增为主要特征 [1―2] 。尽管化
一种异质性血液系统恶性肿瘤,以骨髓、血液和其他组 疗手段有所进展,但 AML 患者预后仍然较差 。因此,
[3]
有必要进一步了解 AML 的相关机制并寻找新型治疗
Δ 基金项目 山 东 省 医 药 卫 生 科 技 发 展 计 划 项 目(No. 2019-
WS283) 药物。
*第一作者 主管技师。研究方向:输血检验及血液免疫。E-mail: 虎杖苷(polydatin,PD)是一种从虎杖根中分离出来
huamin1h@163.com
的活性成分,具有抑制血小板聚集、降低血脂水平、减少
# 通信作者 主管技师。研究方向:医学检验。E-mail:xgjz3e@
163.com 脂质过氧化等多种活性。研究发现,PD 可以通过诱导
中国药房 2024年第35卷第6期 China Pharmacy 2024 Vol. 35 No. 6 · 701 ·