Page 73 - 《中国药房》2025年2期
P. 73
欧前胡素调节ThPOK表达对胃癌细胞恶性生物学行为的影响
Δ
1*
1
2 #
1
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
+
+
+
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-
+
+
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
+
+
+
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
1
1
CHEN Lan ,XIA Lingli ,CHEN Ying ,ZHANG Gang ,WEN Feng(1. Dept. of Gastroenterology, Wuhan Sixth
2
1
1
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
+
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 (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
+
T proportion, CD4 T/CD8 T, and the protein expression of ThPOK were decreased or down-regulated significantly (P<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.
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 ·