Department of General, Visceral, and Transplantation Surgery, University of Ulm, Ulm, Germany.
Pancreas. 2013 Jan;42(1):141-8. doi: 10.1097/MPA.0b013e3182546de5.
Cyclin D1 is important for pancreatic cancer growth. Our aim was to determine the effects of cyclin D1 inhibition on the growth of established pancreatic tumors.
PANC-1 cells harboring cyclin D1 antisense cDNA in a tetracycline-inducible vector system were prepared. The effects of cyclin D1 inhibition after tumor development were characterized in a mouse model.
In vitro removal of tetracycline induced cyclin D1 antisense cDNA expression and inhibited cyclin D1 expression and cyclin D1-associated kinase activity as well as anchorage-dependent and -independent growth. After establishment of xenograft tumors in the presence of tetracycline (2 mg/mL) in the drinking water, animals were assigned to either control (tetracycline remained in the drinking water) or to the group without tetracycline for which tetracycline was removed from the drinking water. Tumor growth was significantly inhibited after removal of tetracycline. Microscopic analysis revealed that the area of central necrosis was significantly increased in the group without tetracycline paralleled by a reduction of the vital peripheral area of proliferating cells.
Our results confirmed that cyclin D1 plays an important role in the growth of pancreatic cancer cells and may be an attractive molecular target for the treatment of human pancreatic cancer.
细胞周期蛋白 D1 对胰腺癌的生长很重要。我们的目的是确定细胞周期蛋白 D1 抑制对已建立的胰腺肿瘤生长的影响。
制备了含有四环素诱导型载体系统中细胞周期蛋白 D1 反义 cDNA 的 PANC-1 细胞。在小鼠模型中研究了肿瘤发生后细胞周期蛋白 D1 抑制的作用。
体外去除四环素诱导细胞周期蛋白 D1 反义 cDNA 的表达，并抑制细胞周期蛋白 D1 的表达和细胞周期蛋白 D1 相关激酶活性以及锚定依赖性和非依赖性生长。在饮用水中存在四环素（2mg/mL）的情况下建立异种移植肿瘤后，动物被分为对照组（饮用水中仍保留四环素）或无四环素组，从饮用水中去除四环素。去除四环素后，肿瘤生长明显受到抑制。显微镜分析显示，无四环素组的中央坏死面积显著增加，同时增殖细胞的重要外周区域减少。
我们的结果证实细胞周期蛋白 D1 在胰腺癌细胞的生长中起重要作用，可能是治疗人类胰腺癌的有吸引力的分子靶标。
