SETD7对三阴性乳腺癌阿霉素化疗耐药的作用机制  

Mechanisms of SETD7 in the doxorubicin resistance of triple-negative breast cancer

作　　者：高丽丽[1] 高丝 陈洋[3] 孔宪明 GAO Lili;GAO Si;CHEN Yang;KONG Xianming(School of Health Science and Engineering,University of Shanghai for Science and Technology,Shanghai 200093,China;Renji Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai 200127,China;Dalian Institute of Chemical Physics,Chinese Academy of Sciences,Dalian 116023,China)

机构地区：[1]上海理工大学健康科学与工程学院,上海200093 [2]上海交通大学医学院附属仁济医院,上海200127 [3]中国科学院大连物理化学研究所,大连116023

出　　处：《上海理工大学学报》2025年第1期61-67,共7页Journal of University of Shanghai For Science and Technology

基　　金：国家自然科学基金资助项目(32060209)。

摘　　要：探讨SETD7甲基转移酶在介导三阴性乳腺癌(TNBC)阿霉素化疗耐受中的作用机制。首先,利用CRISPR-Cas9基因编辑技术构建SETD7敲除的TNBC细胞系;然后,通过细胞功能实验(CCK8实验)检测药物敏感性,借助克隆形成实验检测细胞增殖情况,运用流式细胞仪检测细胞凋亡;最后,通过蛋白质免疫印迹法(Western blotting)实验检测凋亡相关蛋白Bcl-2和Bax表达变化。结果表明,SETD7敲除对TNBC增殖活性无明显影响,然而,SETD7敲除或使用SETD7选择性抑制剂(R)-PFI-2增加了TNBC对遗传毒性药物阿霉素的敏感性。在阿霉素处理组中,SETD7敲除的TNBC细胞增殖活性明显降低,凋亡程度更高,且凋亡相关蛋白Bax表达增加,而Bcl-2表达降低。综上,SETD7通过调节Bax和Bcl-2蛋白表达,增强了TNBC阿霉素化疗敏感性。The role of SETD7(su(var)3–9,enhancer of zeste,trithorax-domain-containing protein 7)methyltransferase in mediating doxorubicin chemotherapy resistance in triple-negative breast cancer(TNBC)was explored.First,TNBC cell lines with SETD7 knockout were constructed using CRISPRCas9 gene editing technology.Then,drug sensitivity was assessed through CCK8 assays,cell proliferation was examined via colony formation assays,and apoptosis was measured using flow cytometry.Finally,the levels of apoptosis regulator Bcl-2 and Bax were detected by Western blotting analysis.The results show that SETD7 knockout had no significant impact on TNBC proliferation activity,but SETD7 knockout or the selective inhibitor of SETD7(R)-PFI-2 increased TNBC sensitivity to the chemotherapeutic drug doxorubicin.In the doxorubicin-treated group,SETD7 knockout significantly reduced TNBC cell proliferation,increased apoptosis levels,and upregulated the apoptosis-relating protein Bax while downregulating Bcl-2 expression.In conclusion,SETD7 enhances TNBC doxorubicin chemotherapy sensitivity by regulating the expression of Bax and Bcl-2 proteins.

关 键 词：SETD7 三阴性乳腺癌 阿霉素 化疗耐药 

分 类 号：R730.53[医药卫生—肿瘤]