海参硫酸软骨素抑制小鼠黑色素瘤肺转移作用的研究  

Inhibitory effect of chondroitin sulfate isolated from Isostichopus badionotus on experimental lung metastasis of mouse melanoma cell line

作　　者：李辉[1] 王静凤[1] 张珣[1] 柳东[1] 薛长湖[1] 

机构地区：[1]中国海洋大学食品科学与工程学院,山东青岛266003

出　　处：《中国药理学通报》2011年第5期623-628,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No30871944);海洋公益性行业科研专项(No201105029);国际科技合作项目(No2010DFA31330)

摘　　要：目的海参硫酸软骨素(sea cucumber chondroitin sul-fate,SC-CHS)由美国肉参中分离所得,研究其结构及对小鼠黑色素瘤B16-F10细胞实验性肺转移模型的抑制作用。方法采用MTT法检测了SC-CHS对B16-F10细胞生长的影响;细胞黏附实验研究了SC-CHS对B16-F10细胞黏附能力的影响;体内实验,预先腹腔给药5 d后,建立实验性肺转移模型,继续腹腔注射SC-CHS 20d后,检测小鼠肺转移灶形成,血清中唾液酸的含量、γ-谷氨酰转肽酶活力和肺组织中羟脯氨酸、氨基己糖、糖醛酸的含量。结果实验结果显示SC-CHS体外对B16-F10细胞的生长没有影响,但可以明显降低B16-F10细胞同基质和血管内皮细胞的黏附能力(P<0.05)。SC-CHS剂量组小鼠的肺转移灶数量明显减少(P<0.01),平均转移抑制率为62.66%,血清唾液酸含量和γ-谷氨酰转肽酶活力明显降低(P<0.01),肺组织中羟脯氨酸、氨基己糖、糖醛酸的含量明显下降(P<0.01)。结论 SC-CHS能抑制肿瘤细胞在小鼠体内的转移和生长,其机制可能与降低肿瘤细胞与基质的黏附能力和细胞的转移能力有关。Aim To observe the inhibitory effect of chondroitin sulfate（SC-CHS）isolated from Isostichopus badionotus on lung metastasis of mouse melanoma cell line B16-F10.Methods After treated with different concentrations of SC-CHS at differenttime points,and the proliferation of B16-F10 cells was assessed by MTT assay.Also,effects of SC-CHS on the adhesion ability with the matrigel,hyaluronic acid,ECV304 of B16-F10 cells were estimated by MTT assays.Forty mice were randomly selected and assigned into four groups（ten animals per group）： the normal control group,the model control group,low and high dosage groups（5 and 20 mg·kg^-1 bw）.After treated daily by intraperitoneally injection of SC-CHS or normal saline for 5 days,each mouse except for the normal control group was used to establish experimental lung metastasis models by injecting B16-F10 malignant melanoma cells into the lateral tail vein.The mice were sacrificed after 20 days of tumor induction,blood was collected for separating the serum and the lungs were dissected out to detect metastatic colonies.The levels of serum saliva acid content,γ-GT energy and hydroxyproline,hexosamines and uronic acid levels in lung tissues were also measured,respectively.Results The results suggested that SC-CHS had no effect on B16-F10 cells growth,but significantly reduced the adhesion ability of B16-F10 with matrigel,hyaluronic acid and ECV304（P〈0.05）.SC-CHS clearly suppressed lung metastasis by 65.26% in mice and could reduce the levels of serum saliva acid content and γ-GT energy clearly（P〈0.01）.Biochemical parameters such as hydroxyproline,hexosamines and uronic acid levels in the lung were also reduced clearly（P〈0.01） in the SC-CHS treated animals.Therefore,the results indicated that SC-CHS isolated from the Isostichopus badionotus could inhibit the experimental metastasis of B16-F10 malignant melanoma cells.Conclusions SC-CHS can inhibit the metastasis of B16-F10 metastatic mouse melanoma cells and its mechanism may be that it can inhibit the

关 键 词：海参硫酸软骨素 实验性肺转移 黏附 唾液酸 透明质酸 Γ-谷氨酰转肽酶 糖醛酸 

分 类 号：R-332[医药卫生] R282.74