Laboratory of Veterinary Biochemistry and Immunology, College of Veterinary Medicine, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Oncol Rep. 2013 Sep;30(3):1129-36. doi: 10.3892/or.2013.2564. Epub 2013 Jun 25.
Pancreatic cancer is the fourth most common cause of cancer-related mortality. In the present study, we employed 2 types of therapeutic stem cells expressing cytosine deaminase (CD) with or without human interferon-β (IFN‑β), HB1.F3.CD and HB1.F3.CD.IFN-β cells, respectively, to selectively treat pancreatic cancer. The CD gene converts the non-toxic prodrug, 5-flurorocytosine (5-FC), into the toxic agent, 5-fluorouracil (5-FU). In addition, human IFN-β is a potent cytokine that has antitumor effects. To generate a xenograft mouse model, PANC-1 cells (2x10(6)/mouse) cultured in DMEM containing 10% FBS were mixed with Matrigel and were subcutaneously injected into Balb/c nu/nu mice. In the migration assay, the stem cells expressing the CD or IFN-β gene effectively migrated toward the pancreatic cancer cells, suggesting the presence of chemoattractant factors secreted by the pancreatic tumors. In the co-culture and MTT assay, antitumor activity of the therapeutic stem cells was observed in the presence of 5-FC was shown that the growth of PANC-1 cells was inhibited. Furthermore, these effects were confirmed in the xenograft mouse model bearing tumors originating from PANC-1 cells. Analyses by histological and fluorescence microscopy showed that treatment with the stem cells resulted in the inhibition of pancreatic cancer growth in the presence of 5-FC. Taken together, these results indicate that stem cells expressing the CD and/or IFN-β gene can be used to effectively treat pancreatic cancer and reduce the side-effects associated with conventional therapies.
胰腺癌是癌症相关死亡的第四大常见原因。在本研究中，我们使用了 2 种表达胞嘧啶脱氨酶 (CD) 的治疗性干细胞，分别为 HB1.F3.CD 和 HB1.F3.CD.IFN-β 细胞，以选择性治疗胰腺癌。CD 基因将无毒前药 5-氟胞嘧啶 (5-FC) 转化为有毒药物 5-氟尿嘧啶 (5-FU)。此外，人干扰素-β是一种具有抗肿瘤作用的有效细胞因子。为了生成异种移植小鼠模型，将在含有 10% FBS 的 DMEM 中培养的 PANC-1 细胞 (2x10(6)/只) 与 Matrigel 混合，并皮下注射到 Balb/c nu/nu 小鼠中。在迁移实验中，表达 CD 或 IFN-β 基因的干细胞有效地向胰腺癌细胞迁移，表明胰腺肿瘤分泌的趋化因子的存在。在共培养和 MTT 实验中，在存在 5-FC 的情况下观察到治疗性干细胞的抗肿瘤活性，表明 PANC-1 细胞的生长受到抑制。此外，在源自 PANC-1 细胞的肿瘤的异种移植小鼠模型中证实了这些效果。组织学和荧光显微镜分析表明，在存在 5-FC 的情况下，用干细胞处理导致胰腺癌生长受到抑制。综上所述，这些结果表明表达 CD 和/或 IFN-β 基因的干细胞可用于有效治疗胰腺癌，并减少与传统疗法相关的副作用。
