赖氨匹林抑制乳腺癌细胞增殖的机制初探  

Preliminary study of aspisol inhibition on proliferation of breast cancer cells

作　　者：张月林[1] 李筱俊[1] 郑海伦[1] 吴华璞[1] 祝晓光[1] 

机构地区：[1]安徽蚌埠医学院药学系药理学教研室,安徽蚌埠233030

出　　处：《中国癌症杂志》2007年第10期758-761,共4页China Oncology

基　　金：安徽省教育厅自然科学重点研究项目(NO.2005KJ047ZD)

摘　　要：背景与目的：有研究证实非类固醇类抗炎药（nonsteroidal anti-inflammatotry drugs，NSAIDs）通过抑制环氧合酶（cyclooxygenase，COX）-2干扰致癌作用，但并不是唯一机制。本实验探讨非选择性环氧合酶-2抑制剂赖氨匹林（aspisol）对体外培养的雌激素受体（ER）阴性（MDA-MB-231）和阳性（MCF-7）人乳腺癌细胞增殖的影响及其ERK（extracellular sigal-regulated kinase，细胞外信号调节蛋白激酶）信号通路的影响。方法：应用MTT比色法分析细胞生长抑制作用，流式细胞技术测定凋亡率，Western blot方法检测赖氨匹林对两种乳腺癌细胞外信号调节蛋白激酶（ERK）／磷酸化（P-ERK）的表达的影响。结果：1～10mmol／L赖氨匹林可抑制MDA-MB-231、MCF-7细胞的生长，且其作用具有剂量和时间依赖性，药物浓度越大，时间越长，抑制作用越明显，差异有显著性（P〈0．01）。赖氨匹林（1，5，10mmol／L）作用24h后诱导MDA-MB-231细胞的早期凋亡率分别为（5．76±1．02）％、（10．28±1．95）％、（15．41±2．14）％，与对照组（0．27±0．17）％比较，差异有显著性（P〈0．01），并呈浓度依赖性。赖氨匹林（1，5，10mmol／L）作用24h后诱导MCF-7细胞的早期凋亡率分别为（4．62±1．05）％、（6．86±2．51）％、（11．40±3．56）％，与对照组（0．21±0．11）％相比，差异有显著性（P〈0．01），并呈浓度依赖性。赖氨匹林可不同程度下调两种乳腺癌细胞P-ERK的表达水平（P〈0．01），但不影响总ERK表达（P〉0．05）。结论：赖氨匹林对ER阳性和ER阴性乳腺癌细胞均有抑制增生，诱导凋亡的作用，其作用机制与抑制乳腺癌ERK信号通路有关。Background and purpose： Many studies indicate that nonsteroidal anti-inflammatory drugs （NSAIDs） may inhihit cancer growth, ltowever, the molecular mechanisms may involve different pathway and still remain unclear. The aim of this experiment was to investigate the influence of aspisol against breast cancer lines , including MDA-MB-231（ estrogen receptor-negative）, MCF-7（ estrogen receptor-positive）, and reveal the potential signaling pathway mechanism of aspisol effect on breast cancer lines. Methods： MDA-MB-231 and MCF-7 human breast cancer cell lines were treated with aspisol in vitro. Cell proliferation was evaluated by MTT assay and rate of apoptosis were determined hy flow cytometry. Extracellular signal regulated kinase （ ERK）, phosphor-ERK（P-ERK） protein expressed in breast cancer cell lines were analyzed by Western blot. Results： （1）The results of MTT assay demonstrated that the growth of MDA-MB-231, MCF-7 cells were inhibited By aspisol in a time- and dose- dependent fashion （P 〈0.01）. （2）FCM analysis showed that aspisol could markedly induce apoptosis, early apoptotic rate for the MDA-MB-231 cells exposure to different concentrations of aspisol （ 1, 5, 10 mmool/L） for 24 h were （5.76 ± 1.02） % , （ 10.28 ± 1.95） % , （ 15.41 ± 2. 14） % respectively, there were significant differences compared with control group （0.27 ± 0.17）% , （P 〈 0.01） ： the early apoptotic rate for MCF-7 cells exposured to different concentrations of aspisol （ 1,5, 10 mmool/L） for 24 h were （4.62 ± 1.05） % , （6.86 ± 2.51 ） % , （ 11.40 ± 3.56） % respectively, there were significant differences compared with control group （0.21 ± 0.11） % , （ P 〈 0.01）.（3） Western blot analysis showed that expression of P-ERK protein in breast cancer cells were down-regulated by aspisol in some degree（ P 〈 0.01） but not effect total ERK expression（ P 〉 0.05） . Conclusions： aspisnl inhibits proliferation and induces apoptosis not only in

关 键 词：赖氨匹林 乳腺癌 ERK信号通路 

分 类 号：R737.9[医药卫生—肿瘤] R730.53[医药卫生—临床医学]