[1]张裴,周婧,张歆,等.贝母素乙对人胃癌奥沙利铂耐药细胞的影响及其机制实验研究[J].陕西医学杂志,2026,(8):1043-1051,1057.[doi:DOI:10.3969/j.issn.1000-7377.2026.08.005]
　ZHANG Pei,ZHOU Jing,ZHANG Xin,et al.Effects and mechanism of peiminine on oxaliplatin-resistant human gastric cancer cells[J].,2026,(8):1043-1051,1057.[doi:DOI:10.3969/j.issn.1000-7377.2026.08.005]
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贝母素乙对人胃癌奥沙利铂耐药细胞的影响及其机制实验研究

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年8期
页码:
1043-1051,1057
栏目:
基础研究
出版日期:
2026-08-05

文章信息/Info

Title:
Effects and mechanism of peiminine on oxaliplatin-resistant human gastric cancer cells
作者:
张裴; 周婧; 张歆; 王幻; 李欢欢; 张辉
（新疆医科大学第五附属医院药学部，新疆 乌鲁木齐 830011）
Author(s):
ZHANG Pei; ZHOU Jing; ZHANG Xin; WANG Huan; LI Huanhuan; ZHANG Hui
（Department of Pharmacy,the Fifth Affiliated Hospital of Xinjiang Medical University,Urumqi 830011,China）
关键词:
胃癌; 人胃癌奥沙利铂耐药细胞; 贝母素乙; 丝氨酸/苏氨酸蛋白激酶3; 自噬; 凋亡
Keywords:
Gastric cancer; Oxaliplatin-resistant human gastric cancer cells; Peiminine; Serine/threonine protein kinase 3; Autophagy; Apoptosis
分类号:
R 36
DOI:
DOI:10.3969/j.issn.1000-7377.2026.08.005
文献标志码:
A
摘要:
目的：探讨贝母素乙对人胃癌奥沙利铂（L-OHP）耐药细胞的影响，并探究其作用机制及核心靶点。方法：基于癌症基因组图谱胃癌数据集（TCGA-STAD）和GSE65801数据集筛选胃癌相关差异表达基因，通过GO/KEGG富集分析明确通路关联，交集获得胃癌差异基因、自噬相关基因及贝母素乙靶点的核心基因。多因素Cox回归分析核心基因对胃癌患者预后的影响。SwissDock验证贝母素乙与丝氨酸/苏氨酸蛋白激酶3（AKT3）的分子对接。体外细胞实验将人胃癌细胞L-OHP耐药株HGC-27/L-OHP分为对照组（常规培养，无处理）、L-OHP组（20 μmol/L L-OHP干预）、贝母素乙组（50 μmol/L贝母素乙干预）、L-OHP+贝母素乙组（20 μmol/L L-OHP+50 μmol/L贝母素乙联合干预）、L-OHP+贝母素乙+自噬抑制剂3-甲基腺嘌呤（3MA）组（20 μmol/L L-OHP+50 μmol/L贝母素乙+5 mmol/L 3MA联合干预）。CCK-8法检测细胞增殖能力；Transwell实验检测细胞迁移及侵袭能力；DHE和JC-1染色检测活性氧（ROS）水平及线粒体膜电位；RT-qPCR检测关键基因、自噬及凋亡相关蛋白mRNA表达；Western blot检测关键基因蛋白、自噬及凋亡相关蛋白表达。结果：共筛选出10个核心基因，AKT3为影响胃癌患者预后的独立危险因素，贝母素乙与AKT3分子对接结合能为-9.158 kcal/mol。体外细胞实验显示，与0 μmol/L比较，25、50、100 μmol/L贝母素乙在24、48、72 h的OD450值依次降低（均P＜0.05）。与对照组和L-OHP组比较，贝母素乙组、L-OHP+贝母素乙组HGC-27/L-OHP细胞迁移及侵袭数目、ROS荧光强度、AKT3、α1A肾上腺素能受体（ADRA1A）、激酶插入域受体（KDR）、泛素结合蛋白p62（p62）、B细胞淋巴瘤-2（Bcl-2）mRNA及蛋白表达水平依次降低，JC-1聚合体比例、微管相关蛋白轻链3B（LC3B）、PTEN诱导假定激酶1（PINK1）、苄氯素1（Beclin1）、活化型半胱天冬酶-3（Cleaved Caspase-3）、B细胞淋巴瘤-2相关X蛋白(Bax） mRNA及蛋白表达水平依次升高（均P＜0.05）。与L-OHP+贝母素乙组比较，3MA可逆转上述指标变化。结论：贝母素乙可能通过下调AKT3促进人胃癌L-OHP耐药细胞自噬和凋亡，改善细胞氧化应激与线粒体功能，抑制细胞增殖、迁移及侵袭。
Abstract:
Objective:To investigate the effects of peiminine on oxaliplatin (L-OHP)-resistant human gastric cancer cells,and to explore its underlying mechanism and core target.Methods:Differentially expressed genes related to gastric cancer were screened based on The Cancer Genome Atlas stomach adenocarcinoma dataset (TCGA-STAD) and GSE65801 dataset.GO and KEGG enrichment analyses were performed to clarify pathway correlations,and core genes were obtained from the intersection of gastric cancer differentially expressed genes,autophagy-related genes and peiminine targets.Multivariate Cox regression analysis was used to analyze the prognostic impact of core genes in gastric cancer patients.SwissDock was applied to verify the molecular docking between peiminine and serine/threonine protein kinase 3 (AKT3).In vitro cellular experiments,L-OHP-resistant human gastric cancer HGC-27/L-OHP cells were divided into five groups:control group (routine culture without treatment),L-OHP group (intervention with 20 μmol/L L-OHP),peiminine group (intervention with 50 μmol/L peiminine),L-OHP+peiminine combined group (co-intervention with 20 μmol/L L-OHP and 50 μmol/L peiminine),and L-OHP+peiminine+autophagy inhibitor 3-methyladenine (3MA) group (co-intervention with 20 μmol/L L-OHP,50 μmol/L peiminine and 5 mmol/L 3MA).CCK-8 assay was adopted to detect cell proliferation;Transwell assay was used to evaluate cell migration and invasion abilities;DHE and JC-1 staining were performed to detect reactive oxygen species (ROS) level and mitochondrial membrane potential;RT-qPCR was used to measure mRNA expression of key genes as well as autophagy- and apoptosis-related proteins;Western blot was utilized to detect protein expression of key genes and autophagy- and apoptosis-related proteins.Results:A total of 10 core genes were screened out,among which AKT3 served as an independent risk factor affecting the prognosis of gastric cancer patients.The binding energy of molecular docking between peiminine and AKT3 was -9.158 kcal/mol.In vitro cellular experiments showed that compared with 0 μmol/L peiminine,the OD450 values of cells treated with 25,50 and 100 μmol/L peiminine decreased sequentially at 24 h,48 h and 72 h (all P＜0.05).Compared with the control group and L-OHP group,the number of migrated and invasive HGC-27/L-OHP cells,ROS fluorescence intensity,as well as mRNA and protein expression levels of AKT3,alpha-1A adrenergic receptor (ADRA1A),kinase insert domain receptor (KDR),ubiquitin-binding protein p62 and B-cell lymphoma-2 (Bcl-2) were significantly reduced in the peiminine group and L-OHP+peiminine group;meanwhile,the proportion of JC-1 aggregates,and mRNA and protein expression levels of microtubule-associated protein light chain 3B (LC3B),PTEN-induced putative kinase 1 (PINK1),Beclin1,Cleaved Caspase-3 and Bcl-2-associated X protein (Bax) were elevated sequentially (all P＜0.05).Compared with the L-OHP+peiminine group,3MA reversed all the above changes of indicators.Conclusion:Peiminine may downregulate AKT3 to promote autophagy and apoptosis of L-OHP-resistant human gastric cancer cells,ameliorate cellular oxidative stress and mitochondrial function,and suppress cell proliferation,migration and invasion.

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备注/Memo

备注/Memo:
新疆维吾尔自治区自然科学基金资助项目(2024D01C167)；新疆维吾尔自治区卫生健康科技计划项目(2026001QNKYXM65001774)
更新日期/Last Update: 2026-08-13