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

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 subcutaneouslv 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 nmoI/L,respectively,ever),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 tumom 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 siRNAtreated 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: Oncogenes; Carcinoma,squamous cell; RNA,small interfering; Matrix metalloproteinase 2; Matrix metalloproteinase 9; Xenograft model antitumor assays