4,4'-二甲氧基查耳酮对人胰腺癌细胞增殖的抑制作用及其机制  

Inhibitory effect of 4,4’-dimethoxychalcone on the proliferation of human pancreatic cancer cells and related mechanisms

作　　者：曹开美 王腾飞 陈凤 齐玲 宋美慧 CAO Kai-mei;WANG Teng-fei;CHEN Feng;QI Ling;SONG Mei-hui(College of Pharmacy,Dali University,Dali Yunnan 671000;Department of Gastroenterology,Qingyuan People’s Hospital,Guangzhou Medical University,Qingyuan Guangdong 511500)

机构地区：[1]大理大学药学院,云南大理671000 [2]广州医科大学附属清远医院(清远市人民医院)消化内科,消化病研究所,广东清远511500

出　　处：《中南药学》2025年第1期107-113,共7页Central South Pharmacy

基　　金：广东省基础研究委员会基础与应用基础研究基金项目(No.2021A1515111095);国家自然科学基金项目(No.82203351)。

摘　　要：目的探讨4,4'-二甲氧基查耳酮(DMC)对胰腺癌细胞增殖和凋亡的影响,并阐明其可能的机制。方法取对数生长期的人源胰腺癌PANC-1细胞和MIA PaCa-2细胞分为对照组和DMC处理组,通过CCK-8法检测细胞活力,克隆形成实验检测细胞集落形成能力,EDU法检测细胞增殖能力,Annexin V/PI双染法检测细胞凋亡率,流式细胞术检测活性氧(ROS)的水平。Western blot法检测Cleaved PARP、Bcl-2、Bax、Cleaved Caspase-3等凋亡相关蛋白的表达水平。免疫荧光染色法检测Cleaved Caspase-3的表达情况。结果细胞学实验表明,与对照组相比,DMC处理48 h后,胰腺癌PANC-1细胞和MIA PaCa-2细胞的活力、增殖能力、集落形成能力均降低;PANC-1细胞内产生的ROS增多,细胞凋亡率升高,Cleaved PARP、Bax、Cleaved Caspase-3等蛋白的表达增多,Bcl-2的蛋白表达减少,添加活性氧抑制剂N-乙酰半胱氨酸(NAC)干预后,改善了细胞内ROS的累积,使Cleaved PARP、Bax、Cleaved Caspase-3表达减少,Bcl-2表达增多。结论DMC可抑制人胰腺癌细胞增殖,其机制可能与提高细胞中ROS水平并诱导细胞凋亡有关。Objective To determine the effect of 4,4'-dimethoxychalcone(DMC)on the proliferation and apoptosis of pancreatic cancer cells,and its potential mechanisms.Methods Human pancreatic cancer cell lines PANC-1 and MIA PaCa-2 were cultured at the logarithmic growth phase and divided into a control group and a DMC treatment group.The cell viability was assessed with CCK-8,while the ability to form colonies was evaluated with a cloning assay.Cell proliferation was measured with the EDU method,and the apoptosis rate was determined via Annexin V/PI double staining.Additionally,the levels of reactive oxygen species(ROS)were quantified by flow cytometry.The expression levels of apoptosis-related proteins,such as Cleaved PARP,Bcl-2,Bax,and Cleaved Caspase-3,were analyzed with Western blot.The expression of Cleaved Caspase-3 was evaluated with immunofluorescence staining.Results Cytological experiments showed that,after 48 hours of DMC treatment,the viability,proliferation,and colony-forming abilities of PANC-1 and MIA PaCa-2 cells were substantially reduced as compared with those of the control group.In PANC-1 cells,ROS levels increased,leading to a higher apoptosis rate and elevated expression of proteins such as Cleaved PARP,Bax,and Cleaved Caspase-3,while Bcl-2 expression decreased.However,addition of the ROS inhibitor N-acetylcysteine improved intracellular ROS levels.After the N-acetylcysteine treatment,the expression of Cleaved PARP,Bax,and Cleaved Caspase-3 decreased,while Bcl-2 expression increased.Conclusion DMC can inhibit the proliferation of human pancreatic cancer cells,whose mechanism might involve increased ROS levels and further induction of apoptosis.

关 键 词：4 4'-二甲氧基查耳酮 胰腺癌 细胞增殖 细胞凋亡 活性氧 

分 类 号：R285[医药卫生—中药学] R286[医药卫生—中医学]