南方医科大学学报Issue(7):1048-1052,5.DOI:10.3969/j.issn.1673-4254.2014.07.27
低相对分子质量肝素联合多柔比星对肝癌细胞迁移能力的影响
Effect of low-molecular-weight heparin combined with doxorubicin on hepatocellular cancer cell migration in vitro
摘要
Abstract
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.关键词
肝癌/低相对分子质量肝素/多柔比星/迁移/基质金属蛋白酶-9/基质金属蛋白酶-2/乙酰肝素酶Key words
hepatocellular cancer/low-molecular-weight heparin/doxorubicin/migration/matrix metalloproteinase-9/matrix metalloproteinase-2/heparanase引用本文复制引用
杨克红,马琳艳,程秀,陈超,张梦晓,刘浩,蒋志文..低相对分子质量肝素联合多柔比星对肝癌细胞迁移能力的影响[J].南方医科大学学报,2014,(7):1048-1052,5.基金项目
国家自然科学基金(81000992,81072207);安徽高等学校省级自然科学研究项目(KJ2009B214Z);蚌埠医学院科研项目(BY0820)@@@@Supported by National Natural Science Foundation of China (81000992,81072207) (81000992,81072207)