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多基因联合作用对kallistatin活性增强的研究
  • 期刊名称:中国药学杂志
  • 时间:0
  • 页码:1805-1810
  • 分类:R965[医药卫生—药理学;医药卫生—药学]
  • 作者机构:[1]华侨大学分子药物学研究所,分子药物教育部工程研究中心,福建泉州362021
  • 相关基金:国家自然科学基金项目(30900822);福建省重点项目(2010Y0036);华侨大学校基金(JB-2R1133)
  • 相关项目:基于信号通路模块的microRNA功能预测与验证
中文摘要:

目的加强kallistatin(Kal)这一多功能内源性抗血管生成因子抗肿瘤活性。方法将其他多个基因与Kal联合应用,利用脂质体将带有目的基因的质粒转染入内皮细胞和肿瘤细胞,分析多基因联合治疗对细胞特性的影响。结果Kal对肺癌细胞A549、NCI—H446、SPC—A1都具抑制作用。Kal与Trail或vasostatin(Vas)联合,可加强对SPC—A1细胞的抑制作用,但三者联合该抑制作用并未进一步加强。Kal与angiostatin(Ang)、Vas联合应用可显著增强对血管内皮细胞EVC304生长、迁移以及小管形成的抑制作用。结论Kal基因可与多种类型的基因联合作用,增强对肿瘤细胞和血管内皮细胞的抑制作用,为肿瘤的多基因联合治疗提供了实验基础。

英文摘要:

OBJECTIVE Kallistatin (Kal) is a new endogenous anti-angiogenic factor. It also has a role in anti-inflammation and anti-oxidation. Moreover, it could directly inhibit the proliferation of cancer ce]ls. The aim of this study is to enhance the activities of this multi-functional gene. METHODS Kal together with other genes was co-transfected into cells using lipofectamine 2000 ( Li- po) , and the cell activities were measured via MTT, scratch, transwell and tube formation assays. RESULTS It was found that Kal could inhibit the growth of A549, NCI-H446 and SPC-A1 cells in vitro. The combination of Kal with Trail or vasostatin(Vas) improved the growth inhibitive effect on SPC-A1 cells, but the combination of these three genes failed to further enhance this phenomenon. Moreover, combination of Kal with angiostatin (Ang) or Vas, two other anti-angiogenic factors, enhanced the anti-cancer and anti-angiogen- ic activities of Kal for EVC304 cells. The combination of the three genes had the most significant activities. CONCLUSION The ac- tivities of Kal can be enhanced by using multigene co-transfenction. This study has provided valuable experimental data for the further application of cancer muhigene therapy.

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