基因沉默KRT18蛋白对胰腺癌细胞增殖和凋亡的影响

Effects of Gene Silencing KRT18 on Proliferation and Apoptosis of Pancreatic Cancer Cells

目的探究敲低角蛋白18(KRT18)表达对胰腺癌细胞系增殖和凋亡等生物学行为的影响。方法使用生信分析手段对KRT18进行分析,使用慢病毒感染两种人胰腺癌细胞系SW1990和Panc-1构建KRT18敲低稳系,Western Blot方法验证KRT18敲低效率及蛋白表达水平,细胞增殖实验(CCK8)检测各组中胰腺癌细胞增殖能力,流式细胞仪检测各组中胰腺癌细胞的凋亡情况。结果KRT18在胰腺癌中存在高表达且其高表达与患者预后不良显著相关。在KRT18敲低组中,胰腺癌细胞系的KRT18蛋白表达明显低于阴性对照组。与阴性对照组相比,敲低KRT18细胞P53蛋白表达水平增高,P53相关凋亡信号通路显著激活,细胞增殖能力显著降低,细胞凋亡率显著增加(P<0.05)。结论基因沉默角蛋白KRT18可以显著上调P53蛋白表达并抑制胰腺癌细胞增殖,并促进癌细胞凋亡,KRT18可作为潜在的肿瘤标志物及药物靶点。

Objective To explore the effect of gene silencing keratin 18(KRT18)on the proliferation and apoptosis of pancreatic cancer cells.Methods Bioinformatics was used to analyze the relationship between KRT18 and prognosis.Human pancreatic cancer cell lines SW1990 and Panc-1 were used as research objects to construct KRT18 knockdown stable line.Western Blot was used to verify efficiency and protein expression.Cell proliferation test(CCK8)was used to detect proliferation ability.Flow cytometry was used to detect apoptosis.Results KRT18 was highly expressed in pancreatic cancer samples,and its high expression was significantly associated with poor prognosis.In gene silencing experiment group,KRT18 protein expression of pancreatic cancer cell lines was significantly lower than that of negative control group.Compared with negative control group,P53 expression and P53-related apoptosis signaling pathway were significantly activated,cell proliferation of KRT18 group was significantly reduced,and apoptosis rate was significantly increased(P<0.05).Conclusion Gene silencing keratin KRT18 could significantly up-regulate P53 protein,inhibit proliferation and promote apoptosis of pancreatic cancer cells.KRT18 could be used as a potential tumor marker and drug target.