利培酮抑制结肠癌细胞株SW480生长的作用机制

Mechanisms underlying risperidone-mediated inhibition of cell proliferation in human colon cancer cell line SW480

目的:探讨利培酮对人结肠癌细胞株SW480生长抑制的作用机制及其相关研究.方法:表皮生长因子和利培酮单独或联合作用于SW480细胞,通过蛋白印迹实验观察蛋白激酶B(protein kinase B,PKB)及细胞外信号调节激酶1/2(extracellular signal-regulated kinase1/2,ERK1/2)磷酸化程度,利用RT-PCR判断细胞因子信号转导抑制因子基因表达水平,利用显微镜及细胞计数方法判断细胞生长情况.结果:利培酮抑制人表皮生长因子诱导的结肠癌细胞株SW480细胞的生长;其机制是通过激活ERK1/2的活性并诱导SOCS3的基因的表达,从而抑制PKB的磷酸化,最终抑制SW480的生长.结论:利培酮具有抑制表皮生长因子对人结肠癌细胞株的生长作用.

To investigate whether risperidone has an inhibitory effect on cell proliferation in human colon carcinoma cell line SW480 and to explore the possible mechanisms involved. METHODS： SW480 cells were treated with epidermal growth factor （EGF） with and without risperidone. Phosphorylation levels of protein kinase B （PKB/Akt） and extracellular signal- regulated kinase 1/2 （ERK1/2） were determined by Western blot. Expression of suppressor of cy tokine signaling 3 （SOCS3） mRNA was detected by RT-PCR. Cell proliferation was asSess4d us ing the trypan blue assay.RESULTS： Risperidone could inhibit the prolif- eration of SW480 cells. Treatment with risperidone increased the phosphorylation of ERK1/2 and mRNA level of SOCS3, which may block EGF-induced EGF receptor phosphorylaiton and in turn inhibit PKB phosphorylation. CONCLUSION： Treatment with risperidone sig- nificantly inhibited EGF-mediated proliferation of SW480 cells.