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海参皂苷Echinoside A和ds-Echinoside A抑制小鼠Lewis肺癌生长和转移作用
  • ISSN号:1002-3461
  • 期刊名称:中国海洋药物
  • 时间:0
  • 页码:1-7
  • 分类:R965[医药卫生—药理学;医药卫生—药学]
  • 作者机构:[1]中国海洋大学食品科学与工程学院,山东青岛266003, [2]青岛国家海洋科学研究中心,山东青岛266071
  • 相关基金:海洋公益性行业科研专项(No.201105029); 国际科技合作项目(No.2010DFA31330); 国家自然科学基金(No.30972284); “泰山学者”建设工程专项经费
  • 相关项目:海参岩藻聚糖硫酸酯的可控酶解、结构分析及抗肿瘤活性研究
中文摘要:

目的探讨海参皂苷Echinoside A(EA)和ds-Echinoside A(DSEA)对小鼠肿瘤生长和自发肺转移的抑制作用及机制。方法建立C57BL/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法检测肿瘤组织中半胱氨酸蛋白水解酶3(Cysteine-requiring Aspartate Protease,Caspase 3)、基质金属蛋白酶-2/9(matrix metalloproteinase-2/9,MMP-2/9)、金属蛋白酶组织抑制剂-1/2(tissue inhibitor of metalloproteinase-1/2,TIMP-1/2)、乙酰肝素酶(heparanase,HPA)和血管内皮生长因子(vascular endothelial growth factor,VEGF)mRNA的表达。结果 EA和DSEA均能抑制Lewis肺癌小鼠移植瘤的生长,并显著抑制减少肺表面转移灶结节数。EA和DSEA可以显著提高荷瘤小鼠肿瘤组织中Caspase 3和TIMP-1/2mRNA的表达,降低MMP-2/9、HPA和VEGF mR-NA的表达(P〈0.05,P〈0.01)。结论 EA和DSEA能显著抑制小鼠Lewis肺癌生长和自发性肺转移,其机制可能与诱导肿瘤细胞凋亡,调节细胞外基质(extracellular matrix,ECM)降解相关基因的表达、抑制VEGF的释放,从而抑制肿瘤细胞的转移和血管新生有关。

英文摘要:

Objective To explore the inhibitory effect and mechanism of EA and DSEA on growth and metastasis of Lewis lung carcinoma(LLC) 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 were sacrificed after 21 days.The subcutaneous tumors were weighed to calculate inhibitory rates.The metastatic tumor foci on lung surface in mice were counted to calculate occurrence rate and inhibitory rate of metastases on lung surface.The expressions of MMP-2,MMP-9,TIMP-1,TIMP-2,HPA,VEGF and Caspase 3 mRNA were detected by RT-PCR.Results EA and DSEA significantly reduced LLC tumor growth and the pulmonary metastatic nodules in the surface of lung.RT-PCR assay showed that both EA and DSEA significantly upregulated the expressions of Caspase 3 and TIMP-1/2.EA and DSEA also downregulated the mRNA expressions of HPA,MMPs and VEGF significantly.Conclusion It is suggested that EA and DSEA could prevent the metastasis by inhibitting the expression of ECM degradation related gene and downregulate the VEGF expression of tumor cell.

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期刊信息
  • 《中国海洋药物》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中国药学会
  • 主编:管华诗
  • 地址:青岛市鱼山路5号
  • 邮编:266003
  • 邮箱:zghyyw@oyc.edu.cn
  • 电话:0532-82031949
  • 国际标准刊号:ISSN:1002-3461
  • 国内统一刊号:ISSN:37-1155/R
  • 邮发代号:24-57
  • 获奖情况:
  • 国内外数据库收录:
  • 美国化学文摘(网络版),美国剑桥科学文摘,中国中国科技核心期刊,中国北大核心期刊(2011版)
  • 被引量:8092