血小板衍生生长因子受体β对骨肉瘤细胞株HOS增殖的影响  

Effects of Platelet-Derived Growth Factor Receptor Beta on Proliferation of Osteosarcoma Cell Line HOS

作　　者：邢思宁 唐瑚应 郭佳琪[1] 刘星[1] 汪长东[1] 易发平[1] 刘革力[1] 武向梅[1] Xing Sining;Tang Huying;Guo Jiaqi;Liu Xing;Wang Changdong;Yi Faping;Liu Geli;Wu Xiangmei(Chongqing Medical University,Chongqing,400016)

机构地区：[1]重庆医科大学,重庆400016

出　　处：《基因组学与应用生物学》2020年第6期2820-2826,共7页Genomics and Applied Biology

基　　金：重庆市教委科学技术研究项目(青年项目)(KJQN201900408)资助。

摘　　要：血管形成是肿瘤生长过程中不可或缺的因素。血小板衍生生长因子受体(platelet-derived growth factor receptor,PDGFR)通过与其配体结合刺激新生血管形成,与多种肿瘤的发生发展密切相关。研究表明其亚型PDGFRβ高表达于大多数骨肉瘤病人标本及细胞株中,促进肿瘤增殖,但具体机制仍未明确。在本研究中,分别对HOS骨肉瘤细胞株进行特异性配体PDGFBB刺激处理及小干扰RNA(siRNA)敲降PDGFRβ处理,然后检测其增殖、细胞周期及相关蛋白的表达。结果表明:经过PDGFBB刺激后细胞增殖能力增强;细胞周期结果显示处于G1期的HOS细胞数量增多,S期和G2/M期细胞数量减少,G2期相关蛋白Cyclin B1和CDK1以及G1期相关蛋白CyclinE2和CDK2表达增高,提示PDGFBB可能促进了G2/M期转化。而经siRNA干扰后,PDGFRβ在mRNA和蛋白水平均显示表达量下降;细胞增殖受到抑制。检测细胞周期结果发现在敲降PDGFRβ后,进入S期的细胞数量增加了约9.71%,而G2/M期的细胞数量约减少了6.78%,S期相关蛋白Cyclin A1和CDK2明显降低,提示发生了S期阻滞。因此我们推测,PDGFRβ通过调控细胞周期进程影响骨肉瘤细胞的增殖。本研究为PDGFRβ影响HOS细胞增殖及其潜在机制提供了理论依据,为PDGFRβ可以作为治疗骨肉瘤的潜在治疗靶点提供了理论依据。Angiogenesis is an indispensable factor in tumor growth.Platelet-derived growth factor receptor(PDGFR)stimulates the formation of new blood vessels through ligand binding,which is closely related to the occurrence and development of various tumors.Studies have shown that its subtype PDGFRβis highly expressed in most osteosarcoma patient specimens and cell lines,which promotes tumor proliferation,but the specific mechanism is still unclear.In this study,we performed specific ligand PDGFBB stimulation treatment and small interfering RNA(siRNA)knockdown treatment for PDGFRβon HOS osteosarcoma cell line respectively.Furthermore,proliferation,cell cycle and related protein expression of cells were tested.The result showed that the proliferation of cells were enhanced after PDGFBB stimulation.The results of cell cycle showed that the number of HOS cells in G1 phase was increased,which in S phase and G2/M phase were decreased.G2 phase related proteins Cyclin B1 and CDK1,as well as G1 phase related proteins CyclinE2 and CDK2 were increased.These results suggested that PDGFBB may promote G2/M phase transformation.After the cells was treated with siRNA for PDGFRβ,PDGFRβwas inhibited both on mRNA and protein levels.The proliferation of cellls were inhibited too.The results of cell cycle showed the number of cells entering the S phase was increased by approximately 9.71%,while the number of cells in the G2/M phase was decreased by approximately 6.78%,and the S phase related proteins Cyclin A1 and CDK2 were significantly reduced,suggesting that S-phase block.Therefore,we speculate that PDGFRβaffects the proliferation of osteosarcoma cells by regulating cell cycle progression.This study provides a theoretical basis for PDGFRβto affect HOS cell proliferation and its underlying mechanism,and lays a foundation for PDGFRβto be a potential therapeutic target for osteosarcoma.

关 键 词：骨肉瘤 血小板衍生生长因子受体β 增殖 细胞周期 

分 类 号：R738.1[医药卫生—肿瘤]