Experimental study on hyperbaric oxygen combined with nimustine in targeting human glioma stem cells model
10.3760/cma.j.issn.1009-6906.2017.02.006
- VernacularTitle:高压氧联合尼莫司汀靶向人脑胶质瘤干细胞模型的实验研究
- Author:
Yujun XI
1
;
Jiawei MA
;
Yanping XUE
;
Honghua CAI
;
Yujing SHENG
;
Yanming CHEN
;
Zhaohui LU
;
Bing LIU
;
Cungang DAI
;
Qiang HUANG
;
Jun DONG
Author Information
1. 苏州大学附属第二医院神经外科, 江苏,215004
- Publication Type:Journal Article
- Keywords:
Glioma stem cells;
Hyperbaric oxygen;
Nimustine;
Immune inflammatory reaction;
Mice
- From:
Chinese journal of nautical medicine and hyperbaric medicine
2017;24(2):103-109
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore therapeutic effects of hyperbaric oxygen (HBO) combined with nimustine (ACNU)on human glioma stem cells model,and analyze the related mechanism involved.Methods Balb/c nude mice were inoculated subcutaneously with human glioma stem cell line SU3,then were divided randomly into 4 groups,i.e.,the ACNU group,the HBO group,the ACNU + HBO group and the blank control group.The body weight and tumor volume of the tumor-bearing mice were measured regularly during the experiment.Unisense microelectrode was applied to detect oxygen level in tumor-bearing mice after HBO treatment.Upon completion of treatment,the tumor-beating mice were sacrificed and tumors were weighed.Histomorphological analyses of the transplanted tumors were also performed to analyze hypoxia,necrosis and expression levels of angiogenic related factors.Results Following HBO therapy,the oxygen level in the tumor tissue of the tumor-beating mice was significantly increased(P ＜ 0.01),and necrotic hemorrhage experienced a sharp decrease,when compared with the control group.The tumor weight of the ACNU + HBO group was the lowest(1.43 ± 0.38)g,and statistical differences could be seen,when compared with those of the other 3 groups(P ＜0.05.Tumor inhibition rates of the ACNU + HBO group,the ACNU group and the HBO group were respectively 76.29％,43.79％ and 31.51％.The expression levels of TNF-α,HIF-1α,NF-κB and VEGF and the density of inflammatory cell infiltration were negatively correlated with tumor inhibition rate.Conclusions HBO therapy could alter the hypoxic microenvironment in which tumor stem cells survive,and could also inhibit tumor cell proliferation and tumor-related inflammatory cell infiltration triggered by glioma stem cells to a certain extent.Besides,combined HBO therapy could improve the curative effect of ACNU,and reverse the hypoxia micro-environment of tumor stem cell niche via negative regulation on the expressions of NF-κB,HIF-1α,TNF-α and VEGF.
