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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 ·
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