Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou 510120, PR China.
Oncol Rep. 2012 Apr;27(4):1003-10. doi: 10.3892/or.2011.1595. Epub 2011 Dec 19.
The prognosis of pancreatic cancer is still very poor. No specific effective gene therapy for pancreatic cancer has been found. As a key enzyme of the metabolic process of arachidonic acid, cyclooxygenase-2 (COX-2) has been found to be closely related to the tumorigenesis of epithelial cancers. However, the antitumor effect of small interfering RNA (siRNA) targeting COX-2 in pancreatic cancer has not yet been verified. Therefore, the aim of this study was to investigate the effects of COX-2 gene silencing by siRNA on cell proliferation, cell apoptosis, cell cycle and tumorigenicity of pancreatic cancer cells. COX-2 mRNA was detected by RT-PCR and real-time PCR. COX-2 protein was detected by Western blotting. The cell proliferation was measured by cell counting using microscopy. The cell apoptosis and cell cycle were measured by flow cytometry. The tumorigenicity of Capan-2 pancreatic cancer cells transfected with COX-2 siRNA was evaluated using a nude mouse xenograft model. The expression of COX-2 mRNA as well as COX-2 protein were downregulated after COX-2 siRNA transfection. COX-2 siRNA could inhibit the growth of Capan-2 cells significantly by decreasing the cell proliferation, increasing cell apoptosis and regulating cell cycle as well. In vivo experiments demonstrated that the mean volume and weight of subcutaneous xenografts in nude mice derived from Capan-2 cells transfected with COX-2 siRNA were significantly decreased. COX-2 siRNA could inhibit the growth of Capan-2 pancreatic cancer cells and also decrease the tumorigenicity of Capan-2 cells, implicating a new potential therapeutic target in pancreatic cancer.
胰腺癌的预后仍然很差。目前尚未发现针对胰腺癌的特异性有效基因治疗方法。环氧化酶-2（COX-2）作为花生四烯酸代谢过程中的关键酶，与上皮癌的发生密切相关。然而，针对 COX-2 的小干扰 RNA（siRNA）在胰腺癌中的抗肿瘤作用尚未得到验证。因此，本研究旨在探讨 COX-2 基因沉默对胰腺癌细胞增殖、细胞凋亡、细胞周期和致瘤性的影响。通过 RT-PCR 和实时 PCR 检测 COX-2 mRNA，通过 Western blot 检测 COX-2 蛋白。用显微镜细胞计数法测量细胞增殖，用流式细胞术测量细胞凋亡和细胞周期。用裸鼠异种移植模型评估转染 COX-2 siRNA 的 Capan-2 胰腺癌细胞的致瘤性。COX-2 siRNA 转染后 COX-2 mRNA 和 COX-2 蛋白的表达均下调。COX-2 siRNA 可通过降低细胞增殖、增加细胞凋亡和调节细胞周期显著抑制 Capan-2 细胞的生长。体内实验表明，转染 COX-2 siRNA 的 Capan-2 细胞来源的裸鼠皮下异种移植的平均体积和重量明显降低。COX-2 siRNA 可抑制 Capan-2 胰腺癌细胞的生长，并降低 Capan-2 细胞的致瘤性，提示其可能成为胰腺癌的新的潜在治疗靶点。
