关键词: 结直肠癌, LS174T, 胸苷磷酸化酶, 5’-脱氧氟尿苷, 干扰素-α2a

Abstract: Background and purpose: In colorectal cancer tissues, little thymidine phosphorylase (TP) expression was detected. In this study, the inhibitory effects of 5’-deoxy-5-fluorouridine (5’-DFUR) and 5-fluorouracil (5-FU) combined with interferon-α2a (INF-α2a) on nude mice transplanted with colorectal cancer cell line LS174T carrying TP cDNA were investigated. Methods: TP cDNA was transfected into human colorectal cancer cell line LS174T with lentiviral vector, and the LS174T cell line with high TP expression was obtained. Then 96 BALB/c nude mice were randomly divided into two groups. Wild LS174T and TP-transfected LS174T (LS174T-TP) cells were inoculated hypodermically into the nude mice back respectively to obtain the colorectal cancer graft models. Two days later, each group was randomly divided into 6 groups again, and different drug interventions were performed continuously for 5 days with normal saline, INF-α2a, 5-FU, 5-FU+INF-α2a, 5’-DFUR and 5’-DFUR+INF-α2a, respectively. All the nude mice were executed after 2 weeks, and tumor tissues were dissected and weighed. The tumor tissue specimens were immunohistochemically stained using the mouse anti-human CD34, VEGF and PDECGF monoclonal antibodies. And then the positive cells and microvessels were quantified respectively. Results: In all of the nude mice transplanted with wild LS174T, the tumor weights of those nude mice injected with antitumor drugs (group 3-6) were significantly lower compared with the control (normal saline), and their tumor inhibition rates were 48%, 27%, 48% and 57% (P<0.05), respectively. Also the inhibition rates of those mice injected with 5’-DFUR, 5’-DFUR+INF-α2a were 48% and 57%, respectively (P<0.05). The inhibition rates of the mice injected with 5-FU+INF-α2a and 5'-DFUR+INF-α2a were 27% and 57%, respectively (P<0.05). In LS174T-TP-transplanted nude mice, the tumor inhibition rates of the mice injected with 5’-DFUR, 5’-DFUR+INF-α2a were 27% and 48%, respectively (P<0.05). However, there was no efficacious antitumor effect on the mice injected with 5-FU and 5-FU+INF-α2a. Immunohistochemical staining showed that in tumor tissues of the mice transplanted with wild LS174T, TP expression was negative and the number of microvessels was significantly less than that in TPtransfected tissues (P<0.05), in which the TP expression was also significantly positive. Conclusion: After colorectal cancer cell line LS174T was transfected with TP cDNA, the TP expression in tumor graft tissues of nude mice was significantly higher than in tumor tissues of those transplanted with wild LS174T. The antitumor effect of 5’-DFUR was significantly enhanced on the nude mice transplanted with LS174T carrying TP cDNA, and it could be futher powered by combination with INF-α2a. However, the antitumor effect of 5-FU, even combined with INF-α2a, was not increased on these nude mouse models.

Key words: Colorectal cancer, LS174T, Thymidine phosphorylasegene, 5’-deoxy-5-fluorouridine, Interferon-α2a