重组人血管内皮抑素联合重组人干扰素γ对小鼠Lewis肺癌移植瘤的作用  

Effects of recombinant human endostatin combined with recombinant human interferon γ on mouse Lewis lung cancer xenografts

作　　者：徐鹏飞 朱玲[1] 万云焱[1] 姚周虹[1] 李德志[1] 王聪 翟聪聪 李文 林殿杰[1] XU Pengfei;ZHU Ling;WAN Yunyan;YAO Zhouhong;LI Dezhi;WANG Cong;ZHAI Congcong;LI Wen;LIN Dianjie(Department of Respiratory and critical care medicine,Shandong Provincial Hospital Affiliated to Shandong University,Jinan 250021,Shandong,China;Department of Respiratory and Critical Care Medicine,Yancheng No.l People's Hospital,Yancheng 224000,Jiangsu,China;Department of Respiratory and Critical Care Medicine,Qilu Hospital of Shandong University,Jinan 250012,Shandong,China;Xuzhou No.5 Cadre's Sanatorium,Xuzhou 2210CK),Jiangsu,China)

机构地区：[1]山东大学附属省立医院呼吸与危重症医学科,山东济南250021 [2]盐城市第一人民医院呼吸与危重症医学科,江苏盐城224000 [3]山东大学齐鲁医院呼吸与危重症医学科,山东济南250012 [4]徐州第五干休所,江苏徐州221000

出　　处：《山东大学学报（医学版）》2020年第1期1-5,12,共6页Journal of Shandong University:Health Sciences

摘　　要：目的探讨重组人内皮抑素(Endostatin)联合重组人干扰素γ(IFNγ)对小鼠Lewis肺癌移植瘤的作用。方法建立小鼠Lewis肺癌移植瘤模型,分为对照组、Endostatin组、IFNγ组和Endostatin+IFNγ组(n均=10),对照组给予鼠磷酸盐缓冲盐水14 d,Endostatin组给予(Endostatin)15 mg/kg·d共14 d、IFNγ组给予(IFNγ)750 IU/kg·d共14 d、Endostatin(15 mg/kg·d)+IFNγ组(750 IU/kg·d)14 d,测量肿瘤的最长径和最短径,计算肿瘤体积。免疫组织化学法测定各组肿瘤组织微血管密度、血管内皮生长因子(VEGF)及低氧诱导因子-1α(HIF-1α)的表达,实时定量RT-PCR法检测VEGF、HIF-1α的表达。结果与对照组比较,Endostatin组、IFNγ组、Endostatin+IFNγ组显示出肿瘤抑制作用(P均<0.001),Endostatin+IFNγ组抑瘤作用最高(P<0.001);Endostatin组、IFNγ组、Endostatin+IFNγ组肿瘤微血管密度降低(P均<0.001),其中Endostatin+IFNγ组肿瘤微血管密度亦较Endostatin组、IFNγ组降低(P<0.001);Endostatin组、IFNγ组、Endostatin+IFNγ组VEGF表达降低(P<0.001),HIF-1α表达升高(P均<0.001),其中Endostatin+IFNγ组变化大(P<0.001)。结论 Endostatin+IFNγ联合治疗可更有效地抑制肿瘤血管生成,并有效抑制肿瘤生长。Objective To investigate the effects of recombinant human endostatin(Endostatin) combined with recombinant human interferon γ(IFNγ) on Lewis lung cancer xenografts in mice. Methods Mice models of Lewis lung cancer xenografts were established and divided into control group, Endostatin group, IFNγ group, and Endostatin+IFNγ group, with 10 mice in each group. The control group was given phosphate buffered saline, Endostatin group was given 15 mg/(kg·d) endostatin, IFNγ group was given 750 IU/(kg·d) IFNγ, and Endostatin+IFNγ group was given 15 mg/(kg·d) endostatin and 750 IU/(kg·d) IFNγ. After 14 days of treatment, the longest and shortest diameters of tumor were measured to calculate tumor volume. The expressions of microvessel density, vascular endothelial growth factor(VEGF) and hypoxic inducible factor-1 α(HIF-1α)were detected with immunohisto chemistry. The expressions of VEGF and HIF-1α were determined with real-time quantitative RT-PCR. Results Compared with the control group, Endostatin, IFNγ and Endostatin+IFNγ groups showed obvious tumor inhibition(P<0.001), and Endostatin+IFNγ group had the most significant tumor inhibition effect(P<0.001). The microvessel density in Endostatin, IFNγ and Endostatin+IFNγ groups all significantly decreased(all P<0.001), and Endostatin+IFNγ group had the lowest density compared with Endostatin and IFNγ groups(P<0.001). The expression of VEGF in Endostatin, IFNγ and Endostatin+IFNγ groups all significantly decreased(P<0.001), while the expression of HIF-1α significantly increased(P<0.001), and the change in Endostatin+IFNγ group was the most significant(P<0.001). Conclusion Combination therapy of endostatin and IFNγ caneffectively inhibits tumor angiogenesis and tumor growth.

关 键 词：血管内皮抑素 干扰素Γ 肺癌 血管生成 

分 类 号：R734.2[医药卫生—肿瘤]