基础医学与临床 ›› 2009, Vol. 29 ›› Issue (10): 1026-1030.

• 研究论文 • 上一篇    下一篇

MMP-28反义寡核苷酸对肺癌细胞生物学行为的影响

张扬 蔺勇 王晓军 吉日嘎拉 哈申高娃   

  1. 吉林大学药学院
  • 收稿日期:2008-11-26 修回日期:2009-01-13 出版日期:2009-10-20 发布日期:2009-10-20

Effect of MMP-28 antisense oligodeoxynucleotide on cell biological behaviour of human lung cancer cell

Yang ZHANG, Yong LIN, Xiao-jun WANG, Jirigala, Hashengaowa   

  1. Pharmacy School, Jilin University
  • Received:2008-11-26 Revised:2009-01-13 Online:2009-10-20 Published:2009-10-20

摘要: 目的 探讨基质金属蛋白酶(MMP)-28反义寡核苷酸(AODN)对人肺癌细胞A549生物学行为的影响。方法 人工合成MMP-28反义寡核苷酸基因,转染至A549细胞,通过半定量RT-PCR和Western blot检测MMP-28 mRNA和蛋白表达;MTT和软琼脂克隆形成实验检测细胞的增殖能力;体外侵袭实验观察细胞体外侵袭能力;裸鼠移植瘤模型观察肺癌细胞形成能力和转移潜能的改变。结果 转染48 h后,与空白对照组和SODN组相比,AODN组细胞MMP-28 mRNA和蛋白表达显著下调(P<0.01);AODN组细胞增殖活性和体外侵袭能力明显下降(P<0.01);AODN组细胞移植瘤重量明显减轻(P<0.01)。结论 MMP-28反义寡核苷酸可明显抑制A549细胞体内、外生长和侵袭,表明MMP-28可能成为肺癌抗侵袭治疗的分子靶点。

关键词: 肺肿瘤, 基质金属蛋白酶, 反义寡核苷酸

Abstract: Objective To study the effect of matrix metalloproteinase (MMP)-28 antisense oligodeoxynucleotide (AODN) on cell biological behaviour of human lung cancer cell A549. Methods To explore its possible functions, cell line A549 was subjected to specific inhibition of MMP-28 by AODN transfection. RT-PCR and Western blot were used to evaluate mRNA and protein level of MMP-28. The proliferative status of cells was measured by MTT assay and soft-agar colony formation assay.Cell invasion ability was detected by Matrigel in vitro invasionassay. The ability of tumor formation and metastatic potency was examined by lung cancer cells xenograft in nude mice. Results After 48 h transfection, the expression of MMP-28 mRNA and protein in AODN-transfected cells was significantly lower than those of control cells and SODN-transfected cells (P<0.01). The ability of proliferation and invasion of AODN-transfected cells was decreased (P<0.01).The weight of xenograft in AODN-transfected cells wasfar less than those of in SODN-transfected cells(P<0.01). Conclusion Both cell proliferation and invasion potential of A549 cells in vitro and in vivo were inhibited effectively by MMP-28 AODN, suggesting that MMP-28 may be a promising molecular target for anti-invasion therapy of human lung cancer.

Key words: lung neoplasms, matrix metalloproteinases, antisense oligodeoxynucleotide

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