海参岩藻聚糖硫酸酯抑制小鼠肿瘤生长和转移及其作用机制的研究

目的探讨海参岩藻聚糖硫酸酯(sea cucumber fu-coidan,SC-FUC)对小鼠肿瘤生长和转移的抑制作用及其机制。方法建立C57 BL/6J小鼠Lewis肺癌自发性肺转移模型,连续腹腔注射给药21 d,剥离原位肿瘤和双侧肺,分别称瘤重和计数肺表面转移灶结节数;采用RT-PCR法检测肿瘤组织中缺氧诱导因子(hypoxia inducible factor-1α,HIF-1α)、血管内皮生长因子(vascular endothelial growth factor,VEGF)、乙酰肝素酶(heparanase,HPA)和基质金属蛋白酶-2/9(matrix metalloproteinase-2/9,MMP-2/9)mRNA的表达。结果 SC-FUC可以抑制荷瘤小鼠肿瘤的生长,其平均抑制率为45.5%,并可以减少肺表面转移灶结节数(P<0.01),平均抑制率为66.0%。SC-FUC可以降低荷瘤小鼠肿瘤组织中HIF-1α、VEGF、HPA、MMP-2/9 mRNA的表达(P<0.05,P<0.01)。结论 SC-FUC能抑制肿瘤细胞在小鼠体内的生长和转移,其机制可能与抑制肿瘤血管新生,降低肿瘤细胞的迁移能力有关。

Anti-metastasis effect of SC-FUC on spontaneous metastasis of mouse Lewis lung carcinoma and its mechanism

Aim To explore the inhibitory effect of sea cucumber fucoidan(SC-FUC) on growth and metastasis of Lewis lung carcinoma in mice.Methods The Lewis lung carcinoma models of C57BL/6J mice were established.Different treatments were served from day 2 after transplantation and all mice killed after 21 days.The subcutaneous tumors were weighed to calculate inhibitory rate.The metastatic tumor foci on lung surface in mice were counted to calculate occurrence rate and inhibition rate of metastases on lung surface.The expressions of HIF-1α,VEGF,HPA,MMP-2,MMP-9 mRNA were detected by RT-PCR.Results The tumor growth was suppressed significantly in SC-FUC low and high groups,the average inhibition rate was 45.5% compared with control group.The metastatic foci occurrence rate of the SC-FUC group was lower than control group,and the difference was significant.The SC-FUC could down-regulate the expression levels of HIF-1α,VEGF,HPA,MMP-2,MMP-9 mRNA more than control.Conclusion SC-FUC has inhibitory effect on growth and metastasis of Lewis lung carcinoma cell in mice,which may be related to the inhibition of solid tumor angiogenesis and the reduction of migrated capacity of the Lewis lung carcinoma cell in vitro.