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欧前胡素调节ThPOK表达对胃癌细胞恶性生物学行为的影响
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          陈 兰 ,夏伶俐 ,陈 颖 ,张 刚 ,文 峰 (1. 江汉大学附属武汉市第六医院消化内科,武汉 430015;
                          1
          2.中部战区总医院消化内科,武汉 430012)
          中图分类号  R965;R735.2      文献标志码  A      文章编号  1001-0408(2025)02-0191-06
          DOI  10.6039/j.issn.1001-0408.2025.02.10

          摘  要  目的  探究欧前胡素(IMP-SD)调节含锌指和 BTB 结构域 7B(ThPOK)表达对胃癌(GC)细胞恶性生物学行为的影响。
          方法  取人GC细胞MKN-7,分为对照组(不给药),IMP-SD低、中、高浓度组(分别给予40、80、160 μmol/L的IMP-SD),si-ThPOK
          和si-NC组[先给予160 μmol/L的IMP-SD,再分别转染ThPOK小分子干扰RNA(si-ThPOK)及其阴性对照(si-NC)])。经相应处理
          后,检测各组细胞的克隆形成、迁移、侵袭能力及凋亡情况,自然杀伤(NK)细胞的杀伤作用,T细胞的分布情况,以及ThPOK、程序
          性死亡受体1(PD-1)及其配体(PD-L1)的表达情况。结果  与对照组比较,IMP-SD各浓度组的细胞克隆数、迁移细胞数、侵袭细胞
          数和PD-1、PD-L1蛋白的表达均显著降低或下调,细胞凋亡率、NK细胞的杀伤活性、CD4  T细胞比例、CD4  T细胞比例与CD8  T
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          细胞比例的比值(CD4  T/CD8  T)、ThPOK蛋白的表达均显著升高或上调,且有浓度依赖性(P<0.05);与IMP-SD高浓度组和si-
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          NC组比较,si-ThPOK组的细胞克隆数、迁移细胞数、侵袭细胞数和PD-L1、PD-1蛋白的表达均显著升高或上调,细胞凋亡率、NK
          细胞的杀伤活性、CD4  T细胞比例、CD4  T/CD8  T、ThPOK蛋白的表达均显著降低或下调(P<0.05)。结论  IMP-SD可能通过促
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          进ThPOK蛋白的表达,从而减弱GC细胞的克隆形成、迁移、侵袭能力,促进其凋亡,抑制其免疫逃逸。
          关键词  欧前胡素;ThPOK;胃癌细胞;免疫逃逸;恶性生物学行为
          Effects  of  imperatorin  on  malignant  biological  behavior  of  gastric  cancer  cells  by  regulating  ThPOK
          expression
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          CHEN Lan ,XIA Lingli ,CHEN Ying ,ZHANG Gang ,WEN Feng(1. Dept. of Gastroenterology, Wuhan Sixth
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          Hospital Affiliated to Jianghan University, Wuhan 430015, China;2. Dept. of Gastroenterology, Central Theater
          Command General Hospital, Wuhan 430012, China)
          ABSTRACT   OBJECTIVE To investigate the effects of imperatorin (IMP-SD) on malignant biological behavior of gastric cancer
         (GC)  cells  by  regulating  zinc  finger  and  BTB  domain  7B (ThPOK).  METHODS  Human  GC  cells  MKN-7  were  used  as  the
          research object and then divided into control group (no treatment), IMP-SD low-, medium- and high-concentration groups (40, 80
          and 160 μmol/L IMP-SD), si-ThPOK and si-NC group [treated with 160 μmol/L IMP-SD and then transfected with ThPOK small
          interfering  RNA (si-ThPOK)  or  its  negative  control (si-NC)].  After  treatment,  cell  clone  formation,  migration  and  invasion
          abilities and apoptosis of MKN-7 cells were detected; the killing activity of NK cells, T cells classification, the protein expressions
          of ThPOK, programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) were all determined. RESULTS Compared with
          the control group, the number of cell clones, migration number, invasion number, and the protein expressions of PD-1 and PD-L1
          were  decreased  or  down-regulated  significantly  in  IMP-SD  groups,  while  the  cell  apoptotic  rate,  NK  cell  killing  activity,  CD4  T
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          proportion,  the  ratio  of  CD4  T  proportion  and  CD8  T  proportion (CD4  T/CD8  T),  and  the  protein  expression  of ThPOK  were
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          increased or up-regulated significantly, in a concentration-dependent manner (P<0.05). Compared with IMP-SD high-concentration
          group and si-NC group, the number of cell clones, migration number, invasion number, and the protein expressions of PD-1 and
          PD-L1 were increased or up-regulated significantly in si-ThPOK group, while the cell apoptotic rate, NK cell killing activity, CD4
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          T  proportion,  CD4   T/CD8   T,  and  the  protein  expression  of  ThPOK  were  decreased  or  down-regulated  significantly (P<0.05).
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          CONCLUSIONS  IMP-SD  may  reduce  the  clonal  formation,  migration  and  invasion  abilities  of  GC  cells,  promote  their  apoptosis
          and inhibit their immune escape by promoting ThPOK expression.
          KEYWORDS    imperatorin; ThPOK; gastric cancer cells; immune escape; malignant biological behavior
             Δ 基金项目 武汉市医学科研项目(No.WX20C29)                        近年来,尽管胃癌(gastric cancer,GC)的发病率和
             *第一作者 副主任医师,硕士。研究方向:消化系统肿瘤。E-
                                                             相关死亡率持续降低,但 2020 年全球新发病例近 109
          mail:15927583670@163.com
                                                             万、死亡病例约 77 万,GC 仍是全球第三大癌症死亡原
             # 通信作者 副主任医师,硕士。研究方向:消化系统肿瘤内镜治
                                                               [1]
          疗。E-mail:n16bgn@163.com                            因 。GC患者确诊时常处于晚期,主要通过手术切除治

          中国药房  2025年第36卷第2期                                                 China Pharmacy  2025 Vol. 36  No. 2    · 191 ·
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