靶向抑制TROP2基因表达对胰腺癌细胞生物学特性的影响研究  

Effect of targeted inhibition of TROP2 gene expression on the biological characteristics of pancreatic cancer cells

作　　者：周童 张远鹏 张启文[1] ZHOU Tong;ZHANG Yuanpeng;ZHANG Qiwen(Department of General Surgery, People＇s Hospital of Laiwu City, Laiwu 271100, Shandong, China)

机构地区：[1]山东省莱芜市人民医院普外科,山东莱芜2711000

出　　处：《癌症进展》2018年第3期290-294,共5页Oncology Progress

摘　　要：目的探讨抑制胰腺癌组织中肿瘤相关钙信号传导因子2(TROP2)表达对胰腺癌细胞增殖和凋亡的影响及机制。方法选取胰腺癌组织和相应的癌旁组织各46例。采用逆转录-聚合酶链反应(RT-PCR)法检测并分析胰腺癌组织和癌旁组织中TROP2基因的m RNA表达情况;将人胰腺癌PANC-1细胞分为对照组、NC-si RNA组和TROP2-si RNA组,培养48 h后,采用蛋白质印迹法检测并分析TROP2、cleaved caspase 3、NOTCH1和HES1蛋白表达情况;采用CCK8法和流式细胞仪分别检测并分析细胞的增殖和凋亡情况。结果在胰腺癌组织中TROP2基因的m RNA表达明显高于癌旁组织,差异有统计学意义(P﹤0.01)。对照组、NC-si RNA组和TROP2-si RNA组中,TROP2蛋白表达、细胞存活率、细胞凋亡率及cleaved caspase 3、NOTCH1、HES1蛋白表达比较,差异均有明显统计学意义(P﹤0.01);TROP2-si RNA组TROP2蛋白表达、细胞存活率及NOTCH1、HES1蛋白表达均明显低于对照组,细胞凋亡率和cleaved caspase 3蛋白表达均明显高于对照组,差异均有统计学意义(P﹤0.01),而NC-si RNA组TROP2蛋白表达、细胞存活率、细胞凋亡率及cleaved caspase 3、NOTCH1、HES1蛋白表达与对照组比较,差异均无统计学意义(P﹥0.05)。结论抑制胰腺癌组织中TROP2基因表达,可以明显降低肿瘤细胞的增殖能力,促进细胞凋亡,其机制与阻断NOTCH1信号通路有关。Objective To investigate the effect of inhibition of tumor-associated calcium signal transducer 2（TROP2） gene expression in pancreatic cancer tissues on the proliferation and apoptosis of cancer cells and the underlying mechanism. Method 46 specimens of pancreatic cancer tissues and adjacent normal tissues each were collected for the analysis. The m RNA expression of TROP2 gene was detected in these specimens by RT-PCR; human pancreatic cancer PANC-1 cells were divided as control group, NC-si RNA group and TROP2-si RNA group, respectively, the expression of TROP2, cleaved caspase 3, NOTCH1 and HES1 proteins were detected after 48 h by Western blot; CCK8 assay and flow cytometry were used to detect the proliferation and apoptosis of cells. Result The m RNA expression of TROP2 gene in pancreatic cancer tissues was significantly higher than that in adjacent tissues, with significant difference observed（P〈0.01）; the expression of TROP2 protein, cell survival rate, expression of cleaved caspase 3, NOTCH1 and HES1 proteins were significantly different among the three groups（P〈0.01）; the TROP2 protein expression, cell survival rate and NOTCH1 and HES1 protein expression in TROP2-si RNA group were significantly lower than those in control group, but the apoptosis rate and cleaved caspase 3 protein expression were significantly higher than those in control（P〈0.01）;while the TROP2 protein expression, cell survival rate, cell apoptosis rate and cleaved caspase 3, NOTCH1, HES1 protein expression in NC-si RNA group were of no significant difference compared with control group（P〈0.01）. Conclusion Inhibition of TROP2 gene expression in pancreatic cancer cells can significantly reduce the proliferation of cancer cells and promote apoptosis, and the mechanism is related to the down regulation of NOTCH1 signaling pathway.

关 键 词：TROP2基因 胰腺癌 NOTCH1信号通路 

分 类 号：R735.9[医药卫生—肿瘤]