PTHR1调控VEGF干预骨肉瘤组织血管形成及增殖的机制研究  

Mechanisms of PTHR1 interfering osteosarcoma angiogenesis and proliferation through regulating VEGF expression

作　　者：岳家吉 李盛龙 孙维超 孙炜[1] Jiaji Yue;Shenglong Li;Weichao Sun;Wei Sun(Department of Joint Surgery and Bone Oncology,The Second People’s Hospitalof Shenzhen,The First Affiliated Hospital of Shenzhen University,Shenzhen 518000,China;Second Ward of Bone and Soft Tissue Surgery,Cancer Hospital of Dalian University of Techno-logy,Liaoning Cancer Hospital&Institute,Shenyang 110042,China)

机构地区：[1]深圳市第二人民医院(深圳大学附属第一医院)骨关节骨肿瘤科,广东省深圳市518000 [2]大连理工大学附属肿瘤医院(辽宁省肿瘤医院)骨与软组织外科二病区

出　　处：《中国肿瘤临床》2023年第7期331-335,共5页Chinese Journal of Clinical Oncology

基　　金：辽宁省自然科学基金项目(编号:2020-MS-058);国家自然科学基金委员会青年基金项目(编号:82003126)资助。

摘　　要：目的:通过分析临床样本构建细胞转染调控模型,分析甲状旁腺激素1型受体(parathyroid hormone type 1 receptor,PTHR1)调控骨肉瘤血管生成和增殖的分子机制,为骨肉瘤的治疗提供新的临床思路。方法:分析2017年1月至2019年12月就诊于大连理工大学附属肿瘤医院(辽宁省肿瘤医院)与深圳市第二人民医院(深圳大学附属第一医院),经组织病理学确认的四肢经典型骨肉瘤患者临床样本共50例,构建PTHR1沉默的骨肉瘤细胞模型,分析PTHR1在肿瘤组织样本中的差异表达,探索PTHR1表达水平与肿瘤增殖及患者生存率之间的相关性。通过体外实验下调PTHR1表达,分析其对血管生成的调控作用。结果:在骨肉瘤患者的临床样本中,PTHR1在肿瘤组织中的表达量显著高于瘤旁组织,且随着PTHR1表达量显著增高,患者肿瘤体积的增大,远期生存率下降。术后36个月生存率,PTHR1高表达组患者显著低于低表达组。在体外实验中,通过沉默PTHR1表达可以有效降低血管生成素血管内皮生长因子(vascular endothelial growth factor,VEGF)表达,抑制肿瘤细胞增殖,在鸡胚胎卵黄囊模型中,抑制骨肉瘤细胞的血管生成能力。结论:PTHR1在肿瘤组织中显著高表达,且与肿瘤增殖及远期生存具有显著相关性,抑制PTHR1可降低骨肉瘤组织血管生成作用。Objective:To provide new clinical ideas for the treatment of osteosarcoma,we analyzed clinical samples and constructed a cell transfection regulation model to examine the molecular mechanisms of parathyroid hormone type 1 receptor(PTHR1)that regulate osteosarcoma angiogenesis and proliferation.Methods:From January 2017 to December 2019,a total of 50 clinical samples taken from patients with classic osteosarcoma of the extremities confirmed by histopathology were examined at Cancer Hospital of Dalian University of Technology(Liaoning Provincial Cancer Hospital)and The Second People’s Hospital of Shenzhen(The First Affiliated Hospital of Shenzhen University).A PTHR1 silent osteosarcoma cell model was constructed,and differential expressions of PTHR1 in tumor tissue samples were analyzed to explore the correlation among PTHR1 expression levels,tumor proliferation,and patient survival rates.PTHR1 expression was downregulated in vitro to analyze its regulatory effect on angiogenesis.Results:In clinical samples of patients with osteosarcoma,PTHR1 expression in tumor tissues was significantly higher than that in adjacent tissues.Significant increases in PTHR1 expression were correlated with increases in tumor volumes and decreases in long-term survival rates.The 3-year cumulative survival rate of patients with high PTHR1 expression was lower than that of patients with low PTHR1 expression.Silencing PTHR1 expression in vitro effectively reduced the expression of vascular endothelial growth factor(VEGF),decreased tumor cells proliferation,and inhibited osteosarcoma angiogenesis in a chicken embryo yolk sac model.Conclusions:PTHR1 is highly expressed in tumor tissue and has a significant correlation with tumor proliferation and long-term survival rates.Inhibiting PTHR1 can reduce angiogenesis in osteosarcoma tissues.

关 键 词：骨肉瘤 甲状旁腺激素 1型受体 增殖 血管生成 

分 类 号：R738.1[医药卫生—肿瘤]