Sun Yun-Peng, Zhang Ben-Long, Duan Jian-Wen, Wu Huan-Huan, Wang Ben-Quan, Yu Zheng-Ping, Yang Wen-Jun, Shan Yun-Feng, Zhou Meng-Tao, Zhang Qi-Yu
Department of Hepatobiliary Surgery, the First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325015, Zhejiang, China.
Department of General Surgery, Yiwu Chouzhou Hospital, Yiwu 322000, Zhejiang, China.
Int J Mol Sci. 2014 Mar 3;15(3):3729-45. doi: 10.3390/ijms15033729.
Pancreatic cancer usually has a poor prognosis, and no gene therapy has yet been developed that is effective to treat it. Since a unique characteristic of bone marrow-derived mesenchymal stem cells (MSCs) is that they migrate to tumor tissues, we wanted to determine whether MSCs could serve as a vehicle of gene therapy for targeting pancreatic cancer. First, we successfully extracted MSCs from SD rats. Next, MSCs were efficiently transduced with NK4, an antagonist of hepatocyte growth factor (HGF) which comprising the N-terminal and the subsequent four kringle domains of HGF, by an adenoviral vector. Then, we confirmed that rat MSCs preferentially migrate to pancreatic cancer cells. Last, MSCs expressing NK4 (NK4-MSCs) strongly inhibited proliferation and migration of the pancreatic cancer cell line SW1990 after co-culture. These results indicate that MSCs can serve as a vehicle of gene therapy for targeting pancreatic cancer.
胰腺癌通常预后较差，目前尚未开发出有效的基因疗法来治疗它。由于骨髓间充质干细胞（MSCs）的一个独特特征是它们会迁移到肿瘤组织，我们想确定MSCs是否可以作为靶向胰腺癌的基因治疗载体。首先，我们成功地从SD大鼠中提取了MSCs。接下来，通过腺病毒载体用NK4（一种肝细胞生长因子（HGF）拮抗剂，由HGF的N端和随后的四个kringle结构域组成）高效转导MSCs。然后，我们证实大鼠MSCs优先迁移到胰腺癌细胞。最后，共培养后，表达NK4的MSCs（NK4-MSCs）强烈抑制胰腺癌细胞系SW1990的增殖和迁移。这些结果表明，MSCs可以作为靶向胰腺癌的基因治疗载体。
