雄激素受体抑制剂通过AR信号通路对胶质瘤生物学特性的影响  

Effects of androgen receptor inhibitor(flutamide) on biological characteristics of glioma via the androgen receptor signaling pathway

作　　者：王长林 牛万祥 程传东 鲍得俊 牛朝诗 

机构地区：[1]安徽医科大学附属省立医院神经外科,安徽合肥230001 [2]脑功能与脑疾病安徽省重点实验室,安徽合肥230001 [3]安徽省脑立体定向神经外科研究所,安徽合肥230001

出　　处：《国际神经病学神经外科学杂志》2018年第1期5-9,共5页Journal of International Neurology and Neurosurgery

基　　金：国家自然科学基金项目(编号:81172407);安徽省自然科学基金项目(编号:1408085MKL69);安徽省科技攻关项目(编号:1604a0802069);脑功能与脑疾病安徽省重点实验室绩效考核补助项目(1606c08235)

摘　　要：目的研究雄激素受体(androgen receptor,AR)抑制剂(flutamide)对人胶质瘤细胞增殖、凋亡、侵袭的影响。方法采用不同浓度的flutamide(低浓度1.0×10^(-8)、中浓度1.0×10^(-7)、高浓度1.0×10^(-6)mol/L)作用于胶质瘤细胞系U251,Real Time-PCR和Western Blot检测AR m RNA及AR蛋白的表达情况;Cell Counting Kit-8法测定flutamide对胶质瘤细胞增殖的影响;Annexin V-7AAD/PE双染检测flutamide诱导胶质瘤细胞凋亡的作用;Transwell测定flutamide对胶质瘤细胞侵袭能力的改变。结果在体外胶质瘤细胞的增殖、侵袭能力能被AR抑制剂(flutamide)显著抑制且凋亡增加,与药物浓度正相关。结论 AR抑制剂(flutamide)能明显抑制胶质瘤细胞的增殖与侵袭,并且诱导细胞凋亡,AR可能是引起胶质瘤发生、发展的危险因素。Objective To investigate the effects of the androgen receptor （AR） inhibitor flutamide on the proliferation, apoptosis, and invasion of human glioma cells in vitro, since AR is overexpressed in glioma tissues and is a risk factor for the development and pro- gression of gliomas. Methods Different concentrations of flutamide （ 1.0 ×10^-8, 1.0 ×10^-7, and 1.0 ×10^-6 mol/L） were added to glioma U251 cells. The mRNA and protein expression of AR was measured by real-time PCR and Western blot, respectively. Cell Counting Kit-8 assay was used to investigate the effect of flutamide on glioma cell proliferation. Flutamide-indnced apoptosis of glioma cells was detected by Annexin V-TAAD/PE staining. The change in glioma cell invasion in the presence of flutamide was evaluated by Transwell assay. Results Flutamide significantly inhibited the proliferation and invasion and increased the apoptosis of U251 cells in vitro, in a dose-dependent manner. Conclusions The AR inhibitor flutamide can significantly inhibit the proliferation and invasion of glioma cells and induce their apoptosis in vitro, and AR may be a risk factor for the development and progression of gliomas.

关 键 词：胶质瘤 雄激素受体 AR抑制剂(flutamide) 增殖 凋亡 

分 类 号：R739.41[医药卫生—肿瘤]