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丹皮酚调控NF-κB/HIF-1α信号通路抑制膀胱癌T24细胞迁移的

          作用及机制
                           Δ


                                                       #
          艾欣瑶 ,陈雯佳,陈 曦,王颖峥,王英豪,黄美霞(福建中医药大学药学院,福州 350122)
                *
          中图分类号  R965      文献标志码  A      文章编号  1001-0408(2025)15-1871-05
          DOI  10.6039/j.issn.1001-0408.2025.15.09

          摘  要  目的  探讨丹皮酚调控核因子κB(NF-κB)/缺氧诱导因子1α(HIF-1α)信号通路介导的有氧糖酵解从而抑制膀胱癌T24细
          胞迁移的作用及机制。方法  将 T24 细胞分为对照组、顺铂组(阳性对照,3.001 μg/mL)和丹皮酚低、中、高剂量组(100、200、
          400 μg/mL),给药干预24 h后,检测丹皮酚对T24细胞迁移能力的影响(以细胞划痕愈合率表示),检测丹皮酚对T24细胞线粒体
          膜电位的影响(以红绿荧光强度比值表示),检测T24细胞中腺苷三磷酸(ATP)浓度和乳酸含量,检测细胞中NF-κB/HIF-1α信号通
          路、迁移相关蛋白以及有氧糖酵解关键酶的表达水平。结果  与对照组比较,丹皮酚中、高剂量组和顺铂组细胞划痕愈合率均显著
          降低(P<0.01);丹皮酚各剂量组细胞中 NF-κB/HIF-1α 信号通路相关蛋白 NF-κB、HIF-1α,迁移相关蛋白基质金属蛋白酶 2
         (MMP2)、MMP9、血管内皮生长因子,有氧糖酵解关键酶葡萄糖转运蛋白1、己糖激酶2、丙酮酸激酶M2表达水平均有不同程度降
          低,大部分差异有统计学意义(P<0.05或P<0.01);丹皮酚中、高剂量组细胞线粒体红绿荧光强度比值均显著降低(P<0.01);丹
          皮酚高剂量组细胞 ATP 浓度以及丹皮酚各剂量组细胞乳酸含量均显著降低(P<0.05 或 P<0.01)。结论  丹皮酚可抑制膀胱癌
          T24细胞的迁移,其作用机制可能与抑制NF-κB/HIF-1α信号通路、下调有氧糖酵解关键酶活性有关。
          关键词  丹皮酚;膀胱癌;NF-κB/HIF-1α信号通路;有氧糖酵解;迁移

          Effect  and  mechanism  of  paeonol  in  regulating  NF-κB/HIF-1α  signaling  pathway  to  inhibit  the  migration
          of bladder cancer T24 cells
          AI Xinyao,CHEN Wenjia,CHEN Xi,WANG Yingzheng,WANG Yinghao,HUANG Meixia(School  of
          Pharmacy, Fujian University of Traditional Chinese Medicine, Fuzhou 350122, China)

          ABSTRACT   OBJECTIVE  To  investigate  the  role  and  mechanism  of  paeonol  in  inhibiting  the  migration  of  bladder  cancer  T24
          cells by regulating nuclear factor κB (NF-κB)/hypoxia-inducible factor-1α (HIF-1α)-mediated aerobic glycolysis. METHODS T24
          cells were divided into control group, cisplatin group (positive control, 3.001 μg/mL), and paeonol low-, medium- and high-dose
          groups (100,  200,  400  μg/mL),  respectively.  After  24  h  of  administration  intervention,  the  effect  of  paeonol  on  the  migration
          ability  of  T24  cells  was  detected (expressed  by  the  cell  scratch  wound  healing  rate).  The  effect  of  paeonol  on  the  mitochondrial
          membrane  potential  of  T24  cells  was  detected (expressed  by  the  ratio  of  red/green  fluorescence  intensity).  Cellular  adenosine
          triphosphate (ATP)  levels  and  lactate  content  in  T24  cells  were  measured.  The  levels  of  NF-κB/HIF-1α  signaling  pathway,  the
          expression  of  migration-related  proteins,  and  key  enzymes  involved  in  aerobic  glycolysis  in  the  cells  were  all  determined.
          RESULTS  Compared  with  the  control  group,  the  cell  scratch  wound  healing  rates  in  the  paeonol  medium-  and  high-dose  groups
          and  the  cisplatin  group  were  decreased  significantly (P<0.01);  in  the  paeonol  groups,  the  expression  levels  of  NF-κB/HIF-1α
          signaling  pathway-related  proteins  such  as  NF- κB  and  HIF-1α,  migration-related  proteins  such  as  matrix  metalloproteinase  2
         (MMP2), MMP9, and vascular endothelial growth factor, as well as key enzymes involved in aerobic glycolysis such as glucose
          transporter 1, hexokinase 2 and pyruvate kinase isozyme type M2, were all reduced to varying degrees in the cells, most of these
          reductions  showed  statistically  significant  differences (P<0.05  or  P<0.01);  the  ratio  of  red/green  fluorescence  intensity  in
          mitochondria of cells in the medium- and high-dose paeonol groups were significantly decreased (P<0.01); the ATP concentration
                                                             in cells of the paeonol high-dose group, and the lactate content
             Δ 基金项目 国家中医药管理局临床中药学高水平中医药重点学                   in  cells  across  all  paeonol  groups  were  significantly  decreased
          科建设项目(No.zyyzdxk-2023107);福建省自然科学基金项目(No.         (P<0.05  or  P<0.01).  CONCLUSIONS  Paeonol  significantly
          2023J01857);福 建 中 医 药 大 学 基 础 类 学 科 科 研 提 升 计 划(No.  inhibits  the  migration  of  bladder  cancer  T24  cells,  and  its
          XJC2022013);福建中医药大学省级财政资助专项(No.X2023005-财          mechanism  of  action  may  be  related  to  the  inhibition  of  the
          政专项)                                               NF-κB/HIF-1α  signaling  pathway,  and  the  down-regulation  of
             *第一作者 硕士研究生。研究方向:中药药理与临床。E-mail:
                                                             key enzyme activities involved in aerobic glycolysis.
          1791876695@qq.com
             # 通信作者 副教授,硕士生导师。研究方向:中药药理与临床。                  KEYWORDS     paeonol;  bladder  cancer;  NF-κB/HIF-1α  sig-
          E-mail:2008009@fjtcm.edu.cn                        naling pathway; aerobic glycolysis; migration


          中国药房  2025年第36卷第15期                                              China Pharmacy  2025 Vol. 36  No. 15    · 1871 ·
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