Choi Sung S, Yoon Kichul, Choi Seon-A, Yoon Seung-Bin, Kim Seung U, Lee Hong J
Biomedical Research Institute, Chung-Ang University College of Medicine, Seoul, Korea.
Seoul Adventist Hospital, Seoul, Korea.
Oncotarget. 2016 Nov 15;7(46):75319-75327. doi: 10.18632/oncotarget.12173.
Advanced pancreatic cancer is one of the most lethal malignant human diseases lacking effective treatment. Its extremely low survival rate necessitates development of novel therapeutic approach. Human neural stem cells (NSCs) are known to have tumor-tropic effect. We genetically engineered them to express rabbit carboxyl esterase (F3.CE), which activates prodrug CPT-11(irinotecan) into potent metabolite SN-38. We found significant inhibition of the growth of BxPC3 human pancreatic cancer cell line in vitro by F3.CE in presence of CPT-11. Apoptosis was also markedly increased in BxPC3 cells treated with F3.CE and CPT-11. The ligand VEGF and receptor VEGF-1(Flt1) were identified to be the relevant tumor-tropic chemoattractant. We confirmed in vivo that in mice injected with BxPC3 on their skin, there was significant reduction of tumor size in those treated with both F3.CE and BxPC3 adjacent to the cancer mass. Administration of F3.CE in conjunction with CPT-11 could be a new possibility as an effective treatment regimen for patients suffering from advanced pancreatic cancer.
晚期胰腺癌是最致命的人类恶性疾病之一，缺乏有效的治疗方法。其极低的生存率使得开发新的治疗方法成为必要。已知人类神经干细胞（NSCs）具有肿瘤趋向性作用。我们对其进行基因工程改造，使其表达兔羧酸酯酶（F3.CE），该酶可将前药CPT-11（伊立替康）激活为强效代谢物SN-38。我们发现，在存在CPT-11的情况下，F3.CE在体外对BxPC3人胰腺癌细胞系的生长有显著抑制作用。用F3.CE和CPT-11处理的BxPC3细胞凋亡也明显增加。配体血管内皮生长因子（VEGF）和受体VEGF-1（Flt1）被确定为相关的肿瘤趋向性趋化因子。我们在体内证实，在皮肤注射BxPC3细胞的小鼠中，在癌块附近同时用F3.CE和BxPC3处理的小鼠肿瘤大小显著减小。联合使用F3.CE和CPT-11可能为晚期胰腺癌患者提供一种有效的新治疗方案。
