The HIF-1α and its related proteins＇ expression in an athymic mouse human neuroblastoma xenograft model

Abstract

Objective To study the HIF-1αand its related proteins＇ expression in an athymicmouse human neuroblastoma xenograh model. Methods The was established by subcutaneous injection of human adrenal neuroblastoma cells. The expressions of HIF-la, VEGF and TGF-α were detected by S-P immunohistochemical techniques. The tumor group was divided into HIF-1α positive group and the HIF-la negative group according to the immunohistochemistry results. The body weight, tumor weight and survival days of the HIF-lapositive mice and HIF-lanegative mice were statistically analyzed. Results Four weeks later, significant neuroblastoma growth occurred in 40 mice （80%）. The positive HIF-1α, VEGF and TGF-α rate of the tumor group was （73.70 ± 10. 68） %, （69. 80 ± 9. 91） %, and （71.43 ± 8. 52） %, respectively. It is significantly increased compared with the control group （P〈0. 01）, which were （9. 67 ± 4. 53） %, （6. 80 ±.40） %, and （6. 50± 4. 44） %, respective-ly. The integrated optical density （IOD） of HIF-1α, VEGF and TGF-a was 141.97 ± 7. 98,151.85 ±14. 35, and 139. 94 ± 4. 50 in tumor group, and 141.34 ± 6. 44, 144. 06 ± 8.51 and 149.00 ±13.63 in positive control group. They were significantly higher than those of the negative control group （P〈 0. 01）. In the tumor group and positive control group, the expression of HIF-1α was positively correla- ted with the expression of VEGF （%2 = 7. 778, r = 0. 504, P〈0. 01）. However, no correlation between the expression of HIF-1α and TGF-a was found（X^2 = 0. 208,r= 0. 934,p〉0. 05）. The body weight, tumor weight and survival days of HIF-1α positive mice were significantly different with those of HIF- 1α negative mice （P〈0. 01）. The mice with positive HIF-1α expression had shorter survival time than the mice with negative HIF-1α （X^2 = 19. 013,P〈0. 05）. Conclusions The athymic mouse human neuroblastoma xenograft model is a good model to research the biology behavior of human neuroblastoma. The overexpression of HIF-1α, VEGF and TGF-1α were found in neuroblastoma which may play important roles in tumor invasion and metastasis. HIF-1α is synergistic with VEGF to promote carcinogenesis. The overexpression of HIF-1α is correlated with poor prognosis. Key words: Hypoxia-inducible factor 1 ; Neuroblastoma; Immunohistochemistry; Mice, Nude