低pH插入肽-蛋白酶激活受体1复合物抑制三阴性乳腺癌MDA-MB-231细胞增殖的实验研究  

The inhibitory effects of pHLIP-P1AP on the proliferation of triple-negative breast cancer MDA-MB-231 cells

作　　者：陈月华 王振光[2] 李大成[2] 于明明[2] CHEN Yuehua;WANG Zhenguang;LI Dacheng;YU Mingming(Intensive Care Unit,the Affiliated Hospital of Qingdao University,Qingdao,266100,Shandong,China;Nuclear Medicine Department,the Affiliated Hospital of Qingdao University,Qingdao,266100,Shandong,China)

机构地区：[1]青岛大学附属医院重症医学科,山东青岛266100 [2]青岛大学附属医院核医学科,山东青岛266100

出　　处：《肿瘤药学》2023年第2期167-172,共6页Anti-Tumor Pharmacy

基　　金：山东省医药卫生科技发展计划项目(202009040347)。

摘　　要：目的观察低pH插入肽-蛋白酶激活受体1(pHLIP-P1AP)复合物对三阴性乳腺癌(TNBC)MDA-MB-231细胞增殖的影响。方法设计、合成荧光标记的pHLIP-P1AP。观察MDA-MB-231细胞与MCF-10A细胞表面蛋白酶激活受体1(PAR1)的表达情况。分析不同pH值(7.4、6.0)条件下荧光标记的pHLIP-P1AP与MDA-MB-231细胞的结合情况及其对MDA-MB-231细胞增殖的影响。结果成功合成了pHLIP-P1AP并进行荧光标记。在酸性环境下(pH 6.0),荧光标记的pHLIP-P1AP与表面高表达PAR1的MDA-MB-231细胞有较强的结合能力,可明显抑制MDA-MB-231细胞的增殖,pHLIP-P1AP为0.5μg、1μg、2μg、4μg、8μg时,细胞的增殖抑制率分别为3.39%,5.27%,14.29%,22.14%、35.69%。结论MDA-MB-231细胞表面表达大量的PAR1。pHLIP-P1AP在酸性环境下能够有效靶向MDA-MB-231细胞,并抑制MDA-MB-231细胞的生长,有望成为治疗TNBC的有价值的新型药物。Objective To observe the effects of pHLIP[pH(low)insertion peptide]-P1AP on the proliferation of triple-negative breast cancer(TNBC)MDA-MB-231 cells.Methods Fluorescent-labeled pHLIP-P1AP was designed and synthe-sized.Protease-activated receptor 1(PAR1)expression on the surface of MDA-MB-231 cells and human MCF10A mam-mary epithelial cells were observed.The binding between fluorescent-labeled pHLIP-P1AP and MDA-MB-231 cells un-der different pH values(pH=7.4,6.0)was analyzed.The effects of pHLIP-P1AP on the proliferation of MDA-MB-231 cells was analyzed under the conditions of pH 7.4 and 6.0.Results pHLIP-P1AP was successfully synthesized and fluorescent-labeled.PAR1 was highly expressed on the surface of MDA-MB-231 cells.In an acidic environment(pH 6.0),fluorescent-labeled pHLIP-P1AP and MDA-MB-231 cells had a high binding ability.In an acidic environment(pH 6.0),pHLIP-P1AP significantly inhibited the proliferation of MDA-MB-231 cells.With 0.5μg,1μg,2μg,4μg,and 8μg of pHLIP-P1AP,the cell proliferation inhibition rates were 3.39%,5.27%,14.29%,22.14%,and 35.69%,respectively.Conclusion PAR1 was highly expressed on the surface of MDA-MB-231 cells.pHLIP-P1AP can effectively target MDA-MB-231 cells in an acidic environment and inhibit the growth of MDA-MB-231 cells.Therefore,pHLIP-P1AP is expected to be a valuable new drug in the treatment of TNBC.

关 键 词：低pH插入肽 蛋白酶激活受体1 三阴性乳腺癌 细胞增殖 

分 类 号：R737.9[医药卫生—肿瘤]