Dumon K R, Ishii H, Vecchione A, Trapasso F, Baldassarre G, Chakrani F, Druck T, Rosato E F, Williams N N, Baffa R, During M J, Huebner K, Croce C M
Kimmel Cancer Center, Thomas Jefferson University, Department of Surgery, Hospital of the University of Pennsylvania, Gene Therapy Center, Jefferson Medical College, Philadelphia, Pennsylvania 19107, USA.
Cancer Res. 2001 Jun 15;61(12):4827-36.
The fragile histidine triad (FHIT) gene is a tumor suppressor gene that is altered by deletion in a large fraction of human tumors, including pancreatic cancer. To evaluate the potential of FHIT gene therapy, we developed recombinant adenoviral and adenoassociated viral (AAV) FHIT vectors and tested these vectors in vitro and in vivo for activity against human pancreatic cancer cells. Our data show that viral FHIT gene delivery results in apoptosis by activation of the caspase pathway. Furthermore, Fhit overexpression enhances the susceptibility of pancreatic cancer cells to exogenous inducers of apoptosis. In vivo results show that FHIT gene transfer delays tumor growth and prolongs survival in a murine model mimicking human disease.
脆性组氨酸三联体（FHIT）基因是一种肿瘤抑制基因，在包括胰腺癌在内的大部分人类肿瘤中会因缺失而发生改变。为了评估FHIT基因治疗的潜力，我们开发了重组腺病毒和腺相关病毒（AAV）FHIT载体，并在体外和体内测试了这些载体对人胰腺癌细胞的活性。我们的数据表明，病毒介导的FHIT基因传递通过激活半胱天冬酶途径导致细胞凋亡。此外，Fhit的过表达增强了胰腺癌细胞对外源性凋亡诱导剂的敏感性。体内实验结果表明，在模拟人类疾病的小鼠模型中，FHIT基因转移可延缓肿瘤生长并延长生存期。
Zotero 插件