Effects of imperatorin on malignant biological behavior of gastric cancer cells by regulating ThPOK expression

CHEN Lan; XIA Lingli; CHEN Ying; ZHANG Gang; WEN Feng

doi:10.6039/j.issn.1001-0408.2025.02.10

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Effects of imperatorin on malignant biological behavior of gastric cancer cells by regulating ThPOK expression

更新时间：2025-09-25

- Effects of imperatorin on malignant biological behavior of gastric cancer cells by regulating ThPOK expression
- ZHONGGUO YAOFANG Vol. 36, Issue 2, Pages: 191-196(2025)
- 作者机构：
  
  1.江汉大学附属武汉市第六医院消化内科，武汉　430015
  2.中部战区总医院消化内科，武汉　430012
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2025.02.10
  CLC： R965;R735.2
- Received：07 June 2024，
  
  Revised：2024-10-16，
  
  Accepted：29 October 2024，
  
  Published：30 January 2025
- 稿件说明：
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陈兰,夏伶俐,陈颖,等.欧前胡素调节ThPOK表达对胃癌细胞恶性生物学行为的影响[J].中国药房,2025,36(02):191-196.

CHEN Lan,XIA Lingli,CHEN Ying,et al.Effects of imperatorin on malignant biological behavior of gastric cancer cells by regulating ThPOK expression[J].ZHONGGUO YAOFANG,2025,36(02):191-196.
陈兰,夏伶俐,陈颖,等.欧前胡素调节ThPOK表达对胃癌细胞恶性生物学行为的影响[J].中国药房,2025,36(02):191-196. DOI： 10.6039/j.issn.1001-0408.2025.02.10.

CHEN Lan,XIA Lingli,CHEN Ying,et al.Effects of imperatorin on malignant biological behavior of gastric cancer cells by regulating ThPOK expression[J].ZHONGGUO YAOFANG,2025,36(02):191-196. 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（

＜0.05）；与IMP-SD高浓度组和si-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（

＜0.05）。

结论

IMP-SD可能通过促进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。

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 proportion， the ratio of CD4

T proportion and CD8

T proportion （CD4

T/CD8

T）， and the protein expression of ThPOK were increased or up-regulated significantly， in a concentration-dependent manner （

＜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 r

ate， NK cell killing activity， CD4

T proportion， CD4

T/CD8

T， and the protein expression of ThPOK were decreased or down-regulated significantly （

＜0.05）.

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.

关键词

Keywords

references

MA X X ， JIA S Q ， WANG G J ， et al . TRIM28 promotes the escape of gastric cancer cells from immune surveillance by increasing PD-L1 abundance [J ] . Signal Transduct Target Ther ， 2023 ， 8 （ 1 ）： 246 .

MAO D L ， ZHOU Z J ， CHEN H X ， et al . Pleckstrin-2 promotes tumor immune escape from NK cells by activating the MT1-MMP-MICA signaling axis in gastric cancer [J ] . Cancer Lett ， 2023 ， 572 ： 216351 .

MILIOTIS C ， MA Y L ， KATOPODI X L ， et al . Determinants of gastric cancer immune escape identified from non-coding immune-landscape quantitative trait loci [J ] . Nat Commun ， 2024 ， 15 （ 1 ）： 4319 .

WU C P ， MURAKAMI M ， LI Y C ， et al . Imperatorin restores chemosensitivity of multidrug-resistant cancer cells by antagonizing ABCG2-mediated drug transport [J ] . Pharmaceuticals ， 2023 ， 16 （ 11 ）： 1595 .

GRABARSKA A ， SKALICKA-WOŹNIAK K ， KIEŁBUS M ， et al . Imperatorin as a promising chemotherapeutic agent against human larynx cancer and rhabdomyosarcoma cells [J ] . Molecules ， 2020 ， 25 （ 9 ）： 2046 .

LV M C ， XU Q X ， ZHANG B ， et al . Imperatorin induces autophagy and G 0 /G 1 phase arrest via PTEN-PI3K-AKT-mTOR/p21 signaling pathway in human osteosarcoma cells in vitro and in vivo [J ] . Cancer Cell Int ， 2021 ， 21 （ 1 ）： 689 .

AM J U ， GONG W J ， SU Y ， et al . Imperatorin shows selective antitumor effects in SGC-7901 human gastric ade-nocarcinoma cells by inducing apoptosis，cell cycle arrest and targeting PI3K/Akt/m-TOR signalling pathway [J ] . J BUON ， 2017 ， 22 （ 6 ）： 1471 - 1476 .

GAO Y Y ， ZAMISCH M ， VACCHIO M ， et al . NuRD complex recruitment to ThPOK mediates CD4 + T cell li-neage differentiation [J ] . Sci Immunol ， 2022 ， 7 （ 72 ）： eabn5917 .

MARIANI F ， SENA ， PEDRONI M ， et al . Th inducing POZ-Krüppel factor（ThPOK）is a key regulator of the immune response since the early steps of colorectal carcinogenesis [J ] . PLoS One ， 2013 ， 8 （ 1 ）： e54488 .

TEREKHOVA M ， SWAIN A ， BOHACOVA P ， et al . Single-cell atlas of healthy human blood unveils age-related loss of NKG2C + GZMB － CD8 + memory T cells and accumulation of type 2 memory T cells [J ] . Immunity ， 2024 ， 57 （ 1 ）： 188 - 192 .

CHEN Y ， JIANG L L ， XIA L L ， et al . ThPOK inhibits the immune escape of gastric cancer cells by inducing STPG1 to inactivate the ERK pathway [J ] . BMC Immunol ， 2022 ， 23 （ 1 ）： 16 .

景红梅，樊海燕，黄小勇，等 . 欧前胡素抑制人肾癌786-O细胞增殖并促进其凋亡 [J ] . 山西医科大学学报， 2023 ， 54 （ 10 ）： 1323 - 1330 .

JING H M ， FAN H Y ， HUANG X Y ， et al . Imperatorin inhibits proliferation and promotes apoptosis of human renal carcinoma cell line 786-O [J ] . J Shanxi Med Univ ， 2023 ， 54 （ 10 ）： 1323 - 1330 .

XU W W ， HUANG Z H ， LIAO L ， et al . Direct targeting of CREB1 with imperatorin inhibits TGF β 2 -ERK signa-ling to suppress esophageal cancer metastasis [J ] . Adv Sci（Weinh）， 2020 ， 7 （ 16 ）： 2000925 .

NUNES-CABAÇO H ， RAMALHO-DOS-SANTOS A ， PIRES A R ， et al . Human CD4 T cells from thymus and cord blood are convertible into CD8 T cells by IL-4 [J ] . Front Immunol ， 2022 ， 13 ： 834033 .

黄丽芳 . 胃癌细胞对CD4 + T细胞ThPOK蛋白表达的影响及其与CD4 + T细胞亚群分化的关系 [D ] . 南昌：南昌大学， 2017 .

HUANG L F . Effect of gastric cancer cells on ThPOK protein expression in CD4 + T cells and its relationship with CD4 + T cell subsets differentiation [D ] . Nanchang ： Nanchang University ， 2017 .

BASU J ， REIS B S ， PERI S ， et al . Essential role of a ThPOK autoregulatory loop in the maintenance of mature CD4 + T cell identity and function [J ] . Nat Immunol ， 2021 ， 22 （ 8 ）： 969 - 982 .

ANDREWS L P ， VIGNALI K M ， SZYMCZAK-WORKMAN A L ， et al . A Cre-driven allele-conditioning line to interrogate CD4 + conventional T cells [J ] . Immunity ， 2021 ， 54 （ 10 ）： 2209 - 2217.e6 .

OUYANG Y ， GU Y ， ZHANG X H ， et al . AMPKα 2 promotes tumor immune escape by inducing CD8 + T-cell exhaustion and CD4 + Treg cell formation in liver hepatocellular carcinoma [J ] . BMC Cancer ， 2024 ， 24 （ 1 ）： 276 .

CHAKRABARTI J ， KOH V ， STEELE N ， et al . Disruption of Her2-induced PD-L1 inhibits tumor cell immune evasion in patient-derived gastric cancer organoids [J ] . Cancers ， 2021 ， 13 （ 24 ）： 6158 .

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