麦冬皂苷B抑制非小细胞肺癌体内迁移机制的研究

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37.5 mg·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、ephrinA1、EphA2、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：OP-B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。

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

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 of A549 cells were observed with HE assay. Meanwhile, Western blot assay was performed to determine the pulmonary levels of Claudin-2, ephrinA1, EphA2, p38MAPK and SAPK/JNK. Results: OP-B at 75 mg·kg-1 significantly inhibited the metastasis of A549 cells in vivo. Meanwhile, it inhibited peripheral blood level of TNF-α and pulmonary level of p-38MAPK at the dose of 75 mg·kg-1 (P<0.01) and upregulated the expression 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.