中华皮肤科杂志 ›› 2011, Vol. 44 ›› Issue (7): 494-496.

• 论著 • 上一篇    下一篇

垂体瘤转化基因小干扰RNA对人皮肤鳞状细胞癌裸鼠移植瘤中基质金属蛋白酶2和9表达的影响

夏永华1,刘冬1,张彩凤2,郭金梅2,李素娟2,付丹丹3,李敏4,李占国2,田中伟5   

  1. 1. 新乡医学院第一附属医院皮肤性病科
    2.
    3. 新乡医学院第一附属医院皮肤科
    4. 河南省人民医院皮肤科
    5. 河南新乡医学院第一附属医院
  • 收稿日期:2010-01-29 修回日期:2010-03-11 出版日期:2011-07-15 发布日期:2011-07-12
  • 通讯作者: 田中伟 E-mail:zhonwt@xxmu.edu.cn
  • 基金资助:

    河南省高校科技创新人才支持计划资助

Effect of PTTG siRNA on MMP-2 and MMP-9 expression in nude mice bearing xenografted human cutaneous squamous cell carcinoma

  • Received:2010-01-29 Revised:2010-03-11 Online:2011-07-15 Published:2011-07-12

摘要:

目的 探讨垂体瘤转化基因(PTTG)小干扰RNA(siRNA)对人皮肤鳞状细胞癌(鳞癌)裸鼠移植瘤生长及浸润和转移相关因子基质金属蛋白酶(MMP)2、9表达的影响。方法 应用人皮肤鳞癌细胞株SCL-1细胞建立裸鼠皮下移植瘤模型,观察经PTTG siRNA治疗后移植瘤的生长情况,并利用RT-PCR和Western印迹检测PTTG siRNA治疗后PTTG、MMP-2及MMP-9 mRNA和蛋白的表达。结果 成功建立人皮肤鳞癌裸鼠皮下移植瘤模型,PTTG siRNA治疗能明显抑制瘤体的生长(P < 0.05),并下调PTTG mRNA和蛋白的表达。此外,PTTG siRNA治疗组中其MMP-2和MMP-9的表达均明显下调。结论 PTTG siRNA能抑制人皮肤鳞癌裸鼠移植瘤的生长,并下调MMP-2和MMP-9表达。

关键词: 基质金属蛋白酶-2/9

Abstract:

Objective To investigate the effect of pituitary tumor-transforming gene (PTTG) siRNA on the growth, invasion of, and expression of metastasis-related cytokines including matrix metalloproteinase-2 (MMP-2) and MMP-9 in xenografted human cutaneous squamous cell carcinoma in nude mice. Methods SCL-1 cells were subcutaneously inoculated into Balb/c nude mice to establish a xenograft model of human cutaneous squamous cell carcinoma. Then, 15 mice bearing xenografted carcinoma were equally divided into 3 groups to be inoculated with phosphate buffer saline (PBS), control siRNA, and PTTG siRNA of 50 nmol/L, respectively, every other day for 2 weeks. The size of xenograted carcinoma in these mice was measured every other day. At the end of 2-week treatment, the mice were killed followed by the evaluation of tumor weight, as well as the quantification of mRNA and protein expression of PTTG, MMP-2 and MMP-9 by reverse transcription (RT)-PCR and Western-blot, respectively. Results The xenograft model of human cutaneous squamous cell carcinoma was successfully established. The treatment with PTTG siRNA obviously inhibited the growth of the xenografted tumors and the expression of PTTG mRNA and protein compared with PBS and control siRNA (all P < 0.05). In addition, the expression of MMP-2 and MMP-9 in xenografted tumors in PTTG siRNA-treated mice were significantly lower than those in PBS and control siRNA-treated mice, suggesting that PTTG siRNA evoked the decrease in invasive and metastatic ability of xenografted tumors. Conclusions PTTG siRNA can inhibit the growth of human cutaneous squamous cell carcinoma xenografts in nude mice, and downregulate the expression of invasion- and metastasis-related cytokines, including MMP-2 and MMP-9.

Key words: matrix metelloproteinase-2/9