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

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

目的探讨垂体瘤转化基因（mG）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FITGsiRNA治疗后移植瘤的生长情况，并利用RT-PCR和Western印迹检测glTGsiRNA治疗后PTrG、MMP-2及MMP-9mRNA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，PTFGsiRNA治疗能明显抑制瘤体的生长（P〈0．05），并下调PTFGmRNA和蛋白的表达。此外，tWFGsiRNA治疗组中其MMP-2和MMP-9的表达均明显下调。结论PTFGsiRNA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。

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 P＇ITG 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 transcrip- tion （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 trITG 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 PTYG 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.