沉默STAT3基因对人胰腺癌细胞体内生长能力的影响

Effect of silencing STAT3 gene on growth of human pancreatic cancer cells in vivo

目的 探讨RNA干扰（RNA interference,RNAi）沉默信号转导与转录激活因子-3（signal transduction and activators 0f transcription,STAT3）对人胰腺癌细胞株SW1990体内生长能力的影响及其机制.方法 构建STAT3短发卡RNA（short hairpin RNA,shRNA）表达载体,稳定转染SW1990细胞,Western blot观察STAT3和磷酸化STAT3（phosphorylated STAT3,p-STAT3）蛋白表达的改变.裸鼠皮下移植瘤模型检测胰腺癌细胞体内生长能力的变化.Western blot检测Bcl-xL和cyclin D1蛋白表达的改变.结果 RNAi后SW1990细胞中STAT3和p-STAT3的蛋白表达分别下降90%和92%（P＜0.05）;裸鼠皮下移植瘤模型显示RNAi沉默STAT3后,SW1990细胞体内生长能力明显下降（P＜0.05）;RT-PCR显示RNAi抑制STAT3后,SW1990细胞中Bcl-xL和cyclin D1的蛋白表达分别降低56%和50%（P＜0.05）.结论 STAT3 shRNA表达载体能有效抑制STAT3基因,并通过下调Bcl-xL和cyclin D1表达,抑制胰腺癌细胞体内生长能力.

Objective To investigate the effect and mechanism of RNAi-mediated STAT3 gene silence on human pancreatic cancer cells growth in vivo. Methods STAT3 shRNA expression vector was stably transfected to SW1990 cells. STAT3 and p-STAT3 protein was examined using Western blot. The growth ability of SW1990 cells in vivo was determined in a subcutaneous tumor model of nude mice. Western blot was performed to detect the protein expression of Bcl-xL and cyclin D1. Results The protein expression of STAT3 and p-STAT3 decreased by 90% and 92% by stable transfection of STAT3 shRNA expressing vectors（P 〈0. 05）. Inhibition of STAT3 with RNAi significantly inhibited the growth ability of SW1990 cells in vivo（ P 〈 0. 05 ）. The tumor weight significantly decreased（ P 〈 0. 05 ）. Moreover, the relative Bcl-xL and cyclinD1 protein expression in SW1990-RNAi cells reduced by 56% and 50% compared with that of the parental SW1990 cells, respectively （P 〈 0. 05）. Conclusions Inhibition of STAT3 with RNAi significantly inhibits the growth ability of pancreatic cancer cells through down-regulating Bcl-xL and cyclin D1.