二氢猕猴桃内酯抑制胃癌细胞增殖的作用机制研究

doi:10.11904/j.issn.1002-3070.2025.02.004

实用肿瘤学杂志 ›› 2025, Vol. 39 ›› Issue (2): 91-98.doi: 10.11904/j.issn.1002-3070.2025.02.004

二氢猕猴桃内酯抑制胃癌细胞增殖的作用机制研究

陈丽娟¹, 马欣欣¹, 高光强¹, 田虹¹, 刘家仁^1,2

1.哈尔滨医科大学附属第四医院检验科(哈尔滨 150001);
2.黑龙江省分子医学工程技术研究中心

收稿日期:2024-10-20 修回日期:2025-03-01 出版日期:2025-04-28 发布日期:2025-05-06
通讯作者: 刘家仁,E-mail:Jiarenliu@hrbmu.edu.cn
作者简介:陈丽娟,女,(1997—),硕士,从事植物化学物在癌症化学预防中的机制研究。
基金资助:
国家自然科学基金(编号:82172580)

Research on the mechanism of dihydroactiniolide in inhibiting the proliferation of gastric cancer cells

CHEN Lijuan¹, MA Xinxin¹, GAO Guangqiang¹, TIAN Hong¹, LIU Jiaren^1,2

1. Department of Clinical Laboratory,The Fourth Affiliated Hospital of Harbin Medical University,Harbin 150001, China;
2. Heilongjiang Molecular Medicine Engineering Technology Research Center

Received:2024-10-20 Revised:2025-03-01 Online:2025-04-28 Published:2025-05-06

摘要/Abstract

摘要： 目的探讨二氢猕猴桃内酯(dihydroactinidiolide,DHAc)抑制胃癌细胞增殖的作用及其可能的机制。方法培养胃癌MKN45细胞和AGS细胞,并分为对照组(不含DHAc的培养液)和不同浓度DHAc(50、100、200、400、600、800、1 000 μmol/L)处理组。使用MTT实验和亚甲蓝(methylene blue,MB)实验检测DHAc对MKN45细胞和AGS细胞活力的影响;通过流式细胞术检测DHAc处理下MKN45细胞线粒体膜电位变化和细胞周期分布,并分析其对AGS细胞周期的影响;利用Western blot技术检测DHAc对MKN45细胞中细胞周期相关蛋白及自噬标志蛋白表达的影响。结果不同浓度DHAc(50、100、200、400、600、800 μmol/L)对胃癌MKN45细胞增殖表现出显著抑制作用,其中,50~400 μmol/L浓度范围的DHAc使MKN45细胞周期阻滞在G0/G1期,并下调细胞周期相关蛋白cyclin D1和CDK4的表达,同时显著降低细胞线粒体膜电位(P＜0.05);在50~200 μmol/L较低浓度范围内,DHAc能够诱导MKN45细胞自噬,表现为LC3-II/LC3-I比值上调(P＜0.05)。另外,不同浓度DHAc(100、200、400、600、800、1 000 μmol/L)也能显著抑制胃癌AGS细胞增殖,其中,100~400 μmol/L浓度范围的DHAc可将AGS细胞周期阻滞在G0/G1期(P＜0.05)。结论 DHAc能够抑制胃癌细胞增殖,可能机制是DHAc阻滞胃癌细胞周期和诱导胃癌细胞自噬发生。

关键词: 二氢猕猴桃内酯, 胃癌细胞, 细胞增殖, 细胞周期, 细胞自噬

Abstract: Objective The aim of this study was to investigate the inhibitory effect of dihydroactinidiolide(DHAc)on proliferation of gastric cancer cells and its possible mechanism. Methods Gastric cancer MKN45 cells and AGS cells were cultured and divided into the control group(culture medium without DHAc)and treatment groups with different concentrations of DHAc(50,100,200,400,600,800,and 1 000 μmol/L).MTT assay and methylene blue(MB)assay were used to detect the effect of DHAc on the viability of MKN45 cells and AGS cells.The changes of mitochondrial membrane potential and the cell cycle distribution of MKN45 cells treated with DHAc were detected by flow cytometry,and its effects on the cell cycle of AGS cells were also analyzed.The effects of DHAc on the expression of proteins related to the cell cycle and autophagy in MKN45 cells were detected by Western blot. Results DHAc at different concentrations of 50,100,200,400,600,and 800 μmol/L showed significant inhibitory effects on proliferation of MKN45 cells.Among them,DHAc at the concentration range of 50-400 μmol/L also arrested the cell cycle of MKN45 cells at the G0/G1 phase,down-regulated the expressions of cyclin D1 and CDK4,and significantly reduced the mitochondrial membrane potential(P＜0.05);In the lower concentration range of 50-200 μmol/L,DHAc could induce autophagy in MKN45 cells,as manifested by the upregulation of the LC3-II/LC3-I ratio(P＜0.05).In addition,different concentrations of DHAc(100,200,400,600,800,and 1 000 μmol/L)could also significantly inhibit the proliferation of AGS cells.Among them,DHAc at the concentration range of 100-400 μmol/L could arrest the cell cycle of AGS cells at the G0/G1 phase(P＜0.05). Conclusion DHAc can inhibit the proliferation of gastric cancer cells.The possible mechanism is that DHAc arrests the cell cycle and induces autophagy in gastric cancer cells.

Key words: Dihydroactinidiolide, Gastric cancer cells, Cell proliferation, Cell cycle, Cell autophagy

中图分类号:

R735.2

陈丽娟, 马欣欣, 高光强, 田虹, 刘家仁. 二氢猕猴桃内酯抑制胃癌细胞增殖的作用机制研究[J]. 实用肿瘤学杂志, 2025, 39(2): 91-98.

CHEN Lijuan, MA Xinxin, GAO Guangqiang, TIAN Hong, LIU Jiaren. Research on the mechanism of dihydroactiniolide in inhibiting the proliferation of gastric cancer cells[J]. Journal of Practical Oncology, 2025, 39(2): 91-98.

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二氢猕猴桃内酯抑制胃癌细胞增殖的作用机制研究

Research on the mechanism of dihydroactiniolide in inhibiting the proliferation of gastric cancer cells

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