异常高表达TCTP通过上调Bcl-xL抑制胰腺癌细胞的细胞凋亡

Aberrant expression of TCTP protein inhibits cell apoptosis by up-regulating Bcl-xL in human pancreatic cancer

背景与目的:胰腺癌是一种常见的恶性肿瘤,病死率高,5年生存率<5%,目前尚无很好的治疗方法。翻译控制肿瘤蛋白(translationally controlled tumor protein,TCTP)是一个生长相关的蛋白质,有促进肿瘤生长,抗细胞凋亡的作用,目前有研究显示TCTP在肝癌、结直肠癌中异常高表达,但其在胰腺癌中的相关研究报道较少。本研究通过对TCTP在胰腺癌细胞中的表达及其生物学作用机制分析,致力于寻找新的肿瘤分子靶点,为胰腺癌的靶向治疗提供依据。方法:采用免疫组织化学方法检测胰腺癌组织中TCTP表达情况;RT-PCR检测胰腺癌细胞株中TCTP的mRNA表达,Western blot方法检测胰腺癌细胞株中TCTP和Bcl-xL蛋白表达水平;免疫荧光染色方法检测TCTP在胰腺癌细胞中的定位;小分子RNA干扰技术沉默胰腺癌细胞中TCTP表达后,利用CCK-8试剂盒检测细胞增殖,流式细胞仪检测胰腺癌细胞的细胞周期和细胞凋亡等生物学指标。结果:与正常胰腺组织相比,胰腺癌组织中TCTP异常高表达,并且主要位于胰腺癌细胞的细胞质中;不同胰腺癌细胞株中TCTP也呈高表达;siRNA沉默胰腺癌细胞中的TCTP,显著抑制细胞的增殖速度和细胞周期进程,促进细胞的凋亡;在胰腺癌细胞中Bcl-xL表达与TCTP表达呈正相关,沉默TCTP可以下调Bcl-xL的蛋白表达。结论:异常高表达TCTP,通过上调Bcl-xL抑制细胞凋亡,从而促进胰腺癌的发生和发展。

Background and purpose： Translationally controlled tumor protein （TCTP） is a growth-related protein, and involves in promoting cell proliferation and inhibiting cell apoptosis. A lot of evidence shows there is an overexpression of TCTP in liver cancer, colon cancer and other gastrointestinal tumors. However there is no any evidence about TCTP in pancreatic cancer. The present study aimed to investigate the role and mechanism of TCTP in pancreatic carcinogenesis to find new molecular targets and to provide a basis for targeted therapy of pancreatic cancer. Methods： Immunohistochemistry, Western immunoblot analysis, RT-PCR, immunofluorescence analysis, siRNA transfection, cell counting kit 8 （CCK-8） assays, cell cycle and cell apoptosis analysis were used. Results： TCTP was overexpressed in pancreatic cancer tissues and cancer cells. Moreover, silencing TCTP expression by siRRA arrested cell cycle progression, promoted cell apoptosis and eventually inhibited cell proliferation. Furthermore, Bcl-xL protein expression was positively correlatived with TCTP expression in pancreatic cancer cells, and silencing TCTP down- regulated Bcl-xL expression. Conclusion： TCTP is overexpressed in human pancreatic cancer, which upregulates Bcl-xL to inhibit cell apoptosis, and eventually promotes pancreatic carcinogenesis.