Molecular Imaging & Therapy Branch, Division of Convergence Technology, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang-si, Gyeonggi-do 410-769, Republic of Korea.
Cancer Lett. 2011 Dec 26;313(1):76-83. doi: 10.1016/j.canlet.2011.08.027. Epub 2011 Sep 3.
Previously, we reported that a novel secretory protein, pancreatic adenocarcinoma up-regulated factor (PAUF), which is highly expressed in pancreatic cancer and mediates the growth and metastasis of pancreatic cancer cells. In this study, we generated and characterized a 2'-fluoropyrimidine modified RNA aptamer (P12FR2) directed against human PAUF. P12FR2 binds specifically to human PAUF with an estimated apparent K(D) of 77nM. P12FR2 aptamer inhibits PAUF-induced migration of PANC-1, human pancreatic cancer cells, in a wound healing assay. Moreover, intraperitoneal injection of P12FR2 decreased tumor growth by about 60% in an in vivo xenograft model with CFPAC-1 pancreatic cancer cells, without causing a loss of weight in the treated mice. Taken together, we propose here that PAUF-specific RNA aptamer, P12FR2, has the potential to be effective in the therapy of human pancreatic cancer.
此前，我们报道了一种新型分泌蛋白，胰腺腺癌上调因子（PAUF），其在胰腺癌中高度表达，并介导胰腺癌细胞的生长和转移。在这项研究中，我们生成并鉴定了一种针对人 PAUF 的 2'-氟嘧啶修饰 RNA 适体（P12FR2）。P12FR2 与人 PAUF 特异性结合，估计表观 K(D)值为 77nM。P12FR2 适体在划痕愈合试验中抑制 PAUF 诱导的 PANC-1 人胰腺癌细胞迁移。此外，在携带 CFPAC-1 胰腺癌细胞的体内异种移植模型中，腹腔内注射 P12FR2 可使肿瘤生长减少约 60%，而接受治疗的小鼠体重没有减轻。综上所述，我们提出 PAUF 特异性 RNA 适体 P12FR2 有可能成为治疗人类胰腺癌的有效方法。
