厄贝沙坦调节SDF-1/CXCR4通路对肺癌细胞增殖、迁移和放射敏感性的影响  

Effects of irbesartan regulating SDF-1/CXCR4 pathway on proliferation,migration and radiosensitivity of lung cancer cells

作　　者：王东娟[1] 连相尧[1] 朱翠敏[1] 吕喜英[1] 林萍萍[1] WANG Dong-juan;LIAN Xiang-yao;ZHU Cui-min;LYU Xi-ying;LIN Ping-ping(Department of Oncology,Affiliated Hospital of Chengde Medical University,Chengde Hebei 067000,China)

机构地区：[1]承德医学院附属医院肿瘤科,河北承德067000

出　　处：《局解手术学杂志》2025年第3期192-198,共7页Journal of Regional Anatomy and Operative Surgery

基　　金：承德市科学技术研究与发展项目(202006A069)。

摘　　要：目的分析厄贝沙坦(IBN)调节基质细胞衍生因子-1(SDF-1)/CXC趋化因子受体4(CXCR4)通路对肺癌细胞增殖、迁移和放射敏感性的影响。方法将人肺癌A549细胞随机分为A549组(不做处理)、放射组(4 Gy X射线照射)、IBN组(1μmol/L IBN处理24 h)、IBN+放射组(1μmol/L IBN处理24 h+4 Gy X射线照射)、pcDNA3.1组(转染pcDNA3.1+1μmol/L IBN处理24 h+4 Gy X射线照射)和SDF-1组(转染pcDNA3.1 SDF-1+1μmol/L IBN处理24 h+4 Gy X射线照射)。观察各组细胞活力、集落形成、凋亡、迁移情况,测定细胞中乳酸脱氢酶(LDH)漏出率和血管紧张素Ⅱ(AngⅡ)水平,采用免疫荧光法分析各组细胞γH2AX焦点形成数,采用蛋白印迹法检测细胞增殖、凋亡相关蛋白及SDF-1/CXCR4通路相关蛋白表达。结果放射和IBN处理均可抑制A549细胞增殖、迁移,促进细胞凋亡,增加γH2AX焦点形成数、LDH漏出率,上调Caspase-3、Bax、Caspase-7表达,下调AngⅡ水平和SDF-1、CXCR4、Bcl-2、PCNA表达(P<0.05);放射和IBN共同处理可进一步增强上述指标变化(P<0.05);SDF-1处理可有效逆转放射和IBN处理对上述指标变化的作用(P<0.05)。结论IBN可通过抑制SDF-1/CXCR4通路,限制肺癌细胞增殖、迁移,并提高放射敏感性。Objective To analyze the effects of irbesartan(IBN)regulating the stromal cell-derived factor-1(SDF-1)/CXC chemokine receptor 4(CXCR4)pathway on proliferation,migration,and radiosensitivity of lung cancer cells.Methods Human lung cancer A549 cells were randomly divided into the A549 group(without treatment),radiation group(4 Gy X-ray radiation),IBN group(1μmol/L IBN treatment for 24 hours),IBN+radiation group(1μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation),pcDNA3.1 group(transfected with pcDNA3.1+1μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation),and SDF-1 group(transfected with pcDNA3.1 SDF-1+1μmol/L IBN treatment for 24 hours+4 Gy X-ray radiation).The cell viability,colony formation,apoptosis,and migration of each group were observed.The leakage rate of lactate dehydrogenase(LDH)and AngⅡlevels in cells were detected.Immunofluorescence method was applied to analyze the number ofγH2AX focal points of cells in each group.Western blot was applied to detect the expression of proliferation and apoptosis related proteins and SDF-1/CXCR4 pathway related proteins.Results Both radiation and IBN treatment inhibited the proliferation and migration of A549 cells,promoted cell apoptosis,upregulated the number ofγH2AX focal points and LDH leakage rate,upregulated the expression of Caspase-3,Bax,and Caspase-7,and downregulated the level of AngⅡand expression of SDF-1,CXCR4,Bcl-2 and PCNA(P<0.05).The combined treatment of radiation and IBN further enhanced the changes of the above indicators(P<0.05).And SDF-1 treatment effectively reversed the effects of radiation and IBN treatment on the changes of the above indicators(P<0.05).Conclusion IBN can limit proliferation and migration of lung cancer cells,and increase radiosensitivity by inhibiting the SDF-1/CXCR4 pathway.

关 键 词：厄贝沙坦 基质细胞衍生因子-1/CXC趋化因子受体4通路 肺癌 增殖 迁移 放射敏感性 

分 类 号：R734.2[医药卫生—肿瘤]