麦冬皂苷B抑制非小细胞肺癌体内迁移机制的研究  

Inhibition Mechanism of Ophiopogonin-B on Metastasis of Non-Small Cell Lung Cancer

作　　者：吴德芹[1] 郭园园[2] 王子川[2] 姜淼[2] 廖子漪 陈美娟[2] WU De-qin;GUO Yuan-yuan;WANG Zi-chuan;JIANG Miao;LIAO Zi-yi;CHEN Mei-juan(The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029;Nanjing University of Chinese Medicine; Jiangsu Collaborative Innovation Center of Traditional Chinese Medicine (TCM) Prevention and Treatment of Tumor, Nanjing 210023)

机构地区：[1]南京医科大学第一附属医院,南京210029 [2]南京中医药大学,江苏省中医药防治肿瘤协同创新中心,南京210023

出　　处：《药学与临床研究》2016年第6期442-444,共3页Pharmaceutical and Clinical Research

基　　金：江苏省自然科学基金(BK20131415);国家自然科学基金(81503374);江苏省高校优势学科建设工程项目(PAPD);欧盟第七框架项目(PIRSES-GA-2013-612589);江苏省教育厅重点项目(16KJA360001)

摘　　要：目的:探究麦冬皂苷B(Ophiopogonin-B,OP-B)抑制非小细胞肺癌细胞株A549体内迁移的作用及其机制。方法:通过对裸鼠进行尾静脉注射A549细胞制成肺转移瘤模型,以37.5mg·kg-1和75 mg·kg-1的剂量进行小鼠的口服灌胃给药21天;ELISA法检测外周血中炎症因子TNF-α、IL^(-1)、IL-6的水平,同时取肺癌组织通过HE染色进行转移灶的观察,结合Western blot法进行Claudin-2、ephrin A1、Eph A2、p-ERK、p-p38MAPK、p-SAPK/JNK的检测,探讨OP-B体内抑制肺癌A549细胞转移的分子机制。结果:高、低剂量OP-B对TNF-α水平均有抑制作用,以高剂量抑制作用更显著;形态学结果表明,高剂量OP-B更能显著抑制A549细胞的体内迁移,同时抑制p38MAPK的磷酸化激活;另外,高、低剂量OP-B均能促进Claudin-2的表达。结论:OPB通过抑制TNF-α的水平进一步抑制p38MAPK的活化,同时上调Claudin-2的表达,抑制A549细胞的裸鼠体内迁移。Objective: To explore the inhibitory effects and mechanisms of ophiopogonin-B (OP-B) on metastasis of non-small cell lung cancer (NSCLC) A549 cells in vivo. Methods: A pulmonary metastasis model was made by injecting A549 cells in nude mice. After OP-B been given (37.5 or 75 mg·kg-1) ig for 21 days, ELISA assay was used to detect blood levels of TNF-α, IL-1 and IL-6. Pulmonary metastasis ofA549 cells were observed with HE assay. Meanwhile, Western blot assay was performed to determine thepulmonary levels of Claudin-2, ephrinA1, EphA2, p38MAPK and SAPK/JNK. Results: OP-B at 75 mg·kg-1significantly inhibited the metastasis of A549 cells in vivo. Meanwhile, it inhibited peripheral blood level ofTNF -α and pulmonary level of p -38MAPK at the dose of 75 mg·kg-1(P <0.01) and upregulated theexpression of Claudin-2 at both doses. Conclusion: OP-B inhibits in vivo metastasis of A549 cells through down-regulation of TNF-α and p-38MAPK phosphorylation and upregulation of Claudin-2.

关 键 词：麦冬皂苷B 非小细胞肺癌 迁移 TNF-Α MAPK Claudin-2 

分 类 号：R965.1[医药卫生—药理学]