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<sup>★</sup>

doi:10.3969/j.issn.2095-1264.2023.02.06

首页 > 过刊浏览>2023年第2期 >167-172. DOI:10.3969/j.issn.2095-1264.2023.02.06

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★
DOI:
                        10.3969/j.issn.2095-1264.2023.02.06
                    
作者:
                        
                        
                    
作者单位: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
作者简介:陈月华，女，硕士，副主任医师，研究方向：内科学。
通讯作者:
中图分类号:R737.9
基金项目:★山东省医药卫生科技发展计划项目（202009040347）。

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

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Affiliation:

1.Intensive Care Unit, the Affiliated Hospital of Qingdao University, Qingdao, 266100, Shandong, China;2.Nuclear Medicine Department, the Affiliated Hospital of Qingdao University, Qingdao, 266100, Shandong, China

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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0.5 μg、1 μg、2 μg、4 μg、8 μg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。

Abstract:

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 synthesized. Protease-activated receptor 1 (PAR1) expression on the surface of MDA-MB-231 cells and human MCF10A mammary epithelial cells were observed. The binding between fluorescent-labeled pHLIP-P1AP and MDA-MB-231 cells under 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 0.5 μg, 1 μg, 2 μg, 4 μg, and 8 μg 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.