STAT3蛋白在三阴性乳腺癌中的作用和临床病理意义

朱清; 张光辉; 赵艳

doi:10.13898/j.cnki.issn.1000-2200.2022.08.002

STAT3蛋白在三阴性乳腺癌中的作用和临床病理意义

Role and clinicopathological significance of STAT3 protein in triple-negative breast cancer

摘要

摘要:
目的探讨组成型激活信号转导激活剂3(STAT3)在三阴性乳腺癌(TNBC)组织中的表达，分析其作为TNBC病人靶向治疗的分子标志物的意义，探究TNBC的发病机制、指导治疗和临床预后。
方法免疫组织化学方法检测STAT3基因在TNBC中的表达并解析其与临床病理的关系。构建STAT3-shRNA表达载体建立下调STAT3基因表达的TNBC细胞系(MDA-MB-231)。CCK-8和Transwell实验验证转染前后MDA-MB-231增殖、侵袭和迁移能力的差异。
结果STAT3蛋白在TNBC中的表达水平显著高于正常乳腺(P < 0.01)，且在TNBC中STAT3阳性表达率与肿瘤体积、组织学分级、TNM分期、淋巴结转移呈正相关(P < 0.05~P < 0.01)。MDA-MB-231细胞转染后实验组STAT3蛋白表达与阴性对照组和空白对照组相比显著降低(P < 0.01)。实验组细胞增殖活性与阴性对照组和空白对照组相比缓慢下降(P < 0.01)。实验组细胞穿过基底膜的数量与阴性对照组和空白对照组比较显著减少(P < 0.01)。
结论STAT3-shRNA表达载体通过RNA干扰有效下调STAT3基因在TNBC中的表达。靶向STAT3-shRNA可抑制MDA-MB-231细胞的增殖、侵袭和迁移及促凋亡能力。

Abstract:
ObjectiveTo investigate the expression of STAT3 in triple-negative breast cancer(TNBC) tissue, analyze its significance as a molecular marker for targeted therapy to TNBC patients, and explore the pathogenesis, clinical efficacy and prognosis of TNBC.
MethodsThe expression of STAT3 gene in TNBC was detected by immunohistochemistry, and its relationship with clinicopathological features was analyzed.The STAT3-shRNA expression vector was constructed to establish a TNBC cell line(MDA-MB-231) with down-regulated STAT3 gene expression.The differences in cell proliferation, invasion and migration abilities before and after transfection were analyzed by CCK-8 and Transwell assay.
ResultsThe expression of STAT3 protein in TNBC tissue was significantly higher than that in breast tissue(P < 0.01), and the positive expression rate of STAT3 in TNBC was positively correlated with tumor volume, histological grade, TNM stage and lymph node metastasis(P < 0.05 to P < 0.01).Compared with the negative control group and blank control group, the expression of STAT3 protein in the experimental group was significantly decreased after transfection in MDA-MB-231 cells, the cell proliferation activity in the experimental group decreased slowly, and the number of cells passing through the basement membrane in the experimental group was significantly reduced(P < 0.01).
ConclusionsThe STAT3-shRNA expression vector effectively down-regulates the expression of STAT3 gene in TNBC by RNA interference.Targeting STAT3-shRNA can inhibit the proliferation, invasion and migration and pro-apoptotic ability of MDA-MB-231 cells.

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