CAJ | 학술논문

目的：探讨低相对分子质量肝素（LMWH）联合多柔比星（DXRB）对肝癌细胞迁移能力的影响及其作用机制。方法实验分为阴性对照组、LMWH组、DXRB组、LMWH与DXRB联合应用组。用MTT法检测药物对HepG2细胞增殖的影响；用细胞划痕实验和Transwell小室法检测HepG2细胞的迁移能力；Western-blot和实时RT-PCR法检测基质金属蛋白酶-9（MMP-9）、基质金属蛋白酶-2（MMP-2）的表达；ELISA法检测肿瘤细胞培养液中乙酰肝素酶的表达。结果 MTT结果显示，LMWH和DXRB对肝癌HepG2细胞均有显著的增殖抑制作用。LMWH与DXRB联合用药时，对肝癌HepG2细胞的迁移抑制作用明显高于单用DXRB组。LMWH和DXRB均可下调MMP-9、MMP-2和乙酰肝素酶的表达，且合用时对乙酰肝素酶表达的抑制作用更明显。结论 LMWH具有增强DXRB抑制肝癌HepG2细胞迁移的作用，其机制可能与下调MMP-9、MMP-2和乙酰肝素酶的表达有关。
목적：탐토저상대분자질량간소（LMWH）연합다유비성（DXRB）대간암세포천이능력적영향급기작용궤제。방법실험분위음성대조조、LMWH조、DXRB조、LMWH여DXRB연합응용조。용MTT법검측약물대HepG2세포증식적영향；용세포화흔실험화Transwell소실법검측HepG2세포적천이능력；Western-blot화실시RT-PCR법검측기질금속단백매-9（MMP-9）、기질금속단백매-2（MMP-2）적표체；ELISA법검측종류세포배양액중을선간소매적표체。결과 MTT결과현시，LMWH화DXRB대간암HepG2세포균유현저적증식억제작용。LMWH여DXRB연합용약시，대간암HepG2세포적천이억제작용명현고우단용DXRB조。LMWH화DXRB균가하조MMP-9、MMP-2화을선간소매적표체，차합용시대을선간소매표체적억제작용경명현。결론 LMWH구유증강DXRB억제간암HepG2세포천이적작용，기궤제가능여하조MMP-9、MMP-2화을선간소매적표체유관。
Objective To investigate the anti- cancer effect of low- molecular- weight heparin (LMWH) combined with doxorubicin and explore the mechanism. Methods Hepatocellular cancer HepG2 cells exposed to LMWH, doxorubicin, or both were evaluated for cell viability with MTT assay and for changes in their migration ability using wound healing assay and Transwell migration assay. The changes in cellular expressions of matrix metalloproteinase-9 (MMP-9) and MMP-2 mRNA and proteins were analyzed with quantitative real-time PCR (qRT-PCR) and Western blotting, and ELISA was used to determine heparanase (HPA) concentration in the cell culture medium. Results HepG2 cells exhibited suppressed proliferation in response to LMWH and doxorubicin treatments. The combined treatment caused a significantly higher inhibition rate of cell migration than LMWH and doxorubicin alone. LMWH enhanced doxorubicin-induced down-regulation of MMP-9, MMP-2 and HPA in the cells. Conclusion LMWH can enhance the inhibitory effect of doxorubicin on the migration of HepG2 cells, the mechanism of which may involve the down-regulation of MMP-9, MMP-2 and HPA expressions.