TIM-3表达对肝癌细胞的作用及其机制研究  

The Expression and mechanism of Tim-3 in hepatocellular carcinoma

作　　者：赵彤 郭海平 郑勤 ZHAO Tong;GUO Hai-ping;ZHENG Qin(Department of Oncology,Nanjing Second Hospital Affiliated to Nanjing University of Traditional Chinese Medicine,Jiangsu 210000,China)

机构地区：[1]南京中医药大学附属南京医院(南京市第二医院),江苏210000

出　　处：《肝脏》2024年第6期671-675,718,共6页Chinese Hepatology

摘　　要：目的 首先明确TIM-3在肝癌组织中的表达,之后在体外细胞水平上探究TIM-3诱发肝癌细胞恶性生物学行为及其可能涉及的作用机制。方法 收集南京市第二医院2021年1月—2021年12月实施肝癌手术治疗的34例原发性肝癌(HCC)癌组织及邻近癌旁组织,采用免疫组织化学法检测肝癌组织中TIM-3的表达情况,分析TIM-3的表达与其临床病理参数的相关性。构建低表达TIM-3的肝癌细胞系验证肝癌细胞增殖迁移能力。Western blot方法探究TIM-3表达及其与Galectin-9的结合对NF-κB/STAT3/IL-6信号轴的影响。结果 肿瘤组织中TIM-3基因的表达为73.5%(25/34),高于癌旁正常组织50%(17/34),差异有统计学意义(χ^(2)=3.985,P=0.046)。在肝癌组织中TIM-3的表达与组织学分型、临床分期有显著相关性(χ^(2)=7.404、5.625,P<0.05)。沉默TIM-3的肝癌细胞增殖率、迁移率(t=12.39、3.129,P<0.05)显著降低。TIM-3的表达上调了NF-κB/STAT3/IL-6相关蛋白,阻断Galectin-9后通路相关蛋白的表达受到抑制。结论 TIM-3在HCC组织中高表达,可促进肝癌细胞的恶性增殖和迁移,TIM-3的表达以及与Galectin-9的相互作用激活IL-6/STAT3/NF-κB信号轴而诱导肝癌细胞恶性生物学进展。Objective To clarify the expression of TIM-3 in hepatocellular carcinoma(HCC)tissues,and investigate the malignant biological behavior of TIM-3-induced HCC cells in vitro and the possible mechanisms involved.Methods A total of 34 patients with primary HCC were enrolled who underwent surgical treatment for HCC from January 2021 to December 2021 in Nanjing Second Hospital.HCC tissues and adjacent neoplastic tissues were collected.The expression of TIM-3 in HCC tissues were detected by immunohistochemistry to analyze the correlation between TIM-3 expression and the clinicopathological parameters.Western blot was used to investigate the effect of TIM-3 expression and its binding to Galectin-9 on NF-κB/STAT3/IL-6 signaling axis.Results The expression of TIM-3 gene in tumor tissues was 73.5%(25/34),which was significantly higher than 50%(17/34)in normal tissues adjacent to cancer(χ^(2)=3.985,P=0.046).The expression of TIM-3 in HCC tissues was significantly correlated with histological staging and clinical stage(χ^(2)=7.404,5.625,P<0.05).The increase rate and migration rateof HCC cells silenced with TIM-3 were significantly reduced(t=12.39,3.129,P<0.05).TIM-3 expression upregulated IL-6/STAT3/NF-κB-related proteins,and the expression of pathway-related proteins was inhibited after blocking Galectin-9.Conclusion TIM-3 is highly expressed in HCC tissues and promotes proliferation and migration of HCC cells.TIM-3 expression and interaction with Galectin-9 induce malignant biological progression of HCC cells by activating the IL-6/STAT3/NF-κB signaling axis.

关 键 词：TIM-3 GALECTIN-9 肝细胞癌 生物学行为 信号通路 

分 类 号：R735.7[医药卫生—肿瘤]