Role of tetrahydrobiopterin in gastric adenocarcinoma progression and lymphangiogenesis

Abstract:

Objective：To investigate the effect of exogenous tetrahydrobiopterin on the growth of subcutaneous tumor graft of MNK-45 gastric adenocarcinoma in BALB/c-nu mice. Methods：Human gastric cancer cell MKN-45 was cultured in vitro，and a subcutaneous transplanted tumor model of human gastric cancer MKN-45 was established in nude mice. Randomized groups were divided into BH4 group and saline group，each with 5 rats. The BH4 group were injected intraperitoneally with BH4（20 mg/kg），once a day for two weeks. Equal volumes of saline were injected in saline group. The changes in tumor growth during treatment were observed. After the treatment，the mice were killed by removing the neck cone，and the tumor was stripped and weighed. The staining extent of inducible nitric oxide synthase（iNOS） and D2-40 was evaluated with immunohistochemical staining，the protein expression was detected with Western blot，nitric oxide（NO） content was determined by Greiss reaction and BH4 content was determined by ELISA analysis. Results：The tumor size in BH4 group was significantly greater than that in saline group（P<0.001）. The contents of BH4 and NO in tumor tissue，and the expression of iNOS and D2-40 were significantly higher in BH4 group than those in saline group（P<0.05）. Conclusion：BH4 may enhance excessive NO synthesis by coupling iNOS，and then induce lymphangiogenesis and promote tumor growth in gastric adenocarcinoma.