Effect of overexpression of hypoxia-inducible factor-1α induced by hyperoxia in vivo in LNCaP tumors on tumor growth rate

摘要

Objective:To study effect of overexpression of hypoxia-inducible factor-1_α induced by hyperoxia in vivo in LNCaP tumors on tumor growth rate.Methods:The prostate cancer LNCaP cells were inoculated in the abdomen of mice.All the mice were randomly placed in the gas chamber with different oxygen content.The groups were divided as follows:twelve mice in hypoxia group,sixteen mice in normoxia group,ten mice in hyperoxia group.After 28 d of treatment,the mice were weighed,the blood samples were taken from the left ventricle,and the tumor was isolated and weighed.Tumor growth,angiogenesis and vascularization,HIF-1_α expression and intracellular signal transduction molecules expression in each group of xenografts were detected and analyzed by using Western blotting and immunofluorescence and determination of hemoglobin.Results:Comparison of the growth of xenografts in each group showed that,the xenografts growth of hypoxia group was more quickly than that of normoxia group.The difference was statistically significant(P=0.Q04).The difference in xenografts growth between hyperoxia group compared and normoxia group was not statistically significant(P>0.05).The expressions of HIF-1_α,VEGF and VEGF-R of xenografts in hyperoxia group were significantly higher than those of normoxia group(P<0.05).The expression of HIF-1_α of xenografts in hypoxia group and normoxia group were similar.The blood growth rate of xenografts in hypoxia group(170%) was significantly higher than that of normoxia group(40%)(P<0.05).The expression of Nrf2 of xenografts in hyperoxia group was significantly higher than that of normoxia group(P<0.05).Conclusions:When hyperoxia induces the overexpression of HIF-1_α in LNCaP tumor,it will not affect tumor growth.It provides a new ideas and theoretical basis for the clinical treatment of prostate cancer.