您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报 (医学版) ›› 2020, Vol. 58 ›› Issue (1): 1-5.doi: 10.6040/j.issn.1671-7554.0.2019.1037

• 基础医学 •    



  1. 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
  • 发布日期:2022-09-27
  • 通讯作者: 林殿杰. E-mail:lindianjie@126.com

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

XU Pengfei1, ZHU Ling1, WAN Yunyan1, YAO Zhouhong1, LI Dezhi1, WANG Cong2, ZHAI Congcong3, LI Wen4, LIN Dianjie1   

  1. 1. Department of Respiratory and critical care medicine, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, Shandong, China;
    2. Department of Respiratory and Critical Care Medicine, Yancheng No.1 People's Hospital, Yancheng 224000, Jiangsu, China;
    3. Department of Respiratory and Critical Care Medicine, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China;
    4. Xuzhou No.5 Cadre's Sanatorium, Xuzhou 221000, Jiangsu, China
  • Published:2022-09-27

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=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<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<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<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。

关键词: 血管内皮抑素, 干扰素γ, 肺癌, 血管生成

Abstract: 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 山 东 大 学 学 报 (医 学 版)58卷1期 -徐鹏飞,等.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 \=-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.

Key words: Endostatin, Interferon γ, Lung cancer, Angiogenesis


  • R734.2
[1] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015[J]. CA Cancer J Clin, 2015, 65(1): 5-29.
[2] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2018[J]. CA Cancer J Clin, 2018, 68(1): 7-30.
[3] Mencoboni M, Filiberti RA, Taveggia P, et al. Safety of first-line chemotherapy with metronomic single-agent oral vinorelbine inelderly patients with NSCLC[J]. Anticancer Res, 2017, 37(6): 3189-3194.
[4] Ham M, Moon A. Inflammatory and microenvironmental factors involved in breast cancer progression[J]. Arch Pharm Res, 2013, 36(12): 1419-1431.
[5] Tartour E, Pere H, Maillere B, et al. Angiogenesis and immunity: a bidirectional link potentially relevant for the monitoring of antiangiogenic therapy and the development of novel therapeutic combination with immunotherapy[J]. Cancer Metastasis Rev, 2011, 30(1): 83-95.
[6] Minn AJ, Wherry EJ. Combination cancer therapies with immune checkpoint blockade: convergence oninterferonsignaling[J]. Cell, 2016, 165(2): 272-275.
[7] Yao D, Shen H, Huang J, et al. Influence of different drug delivery methods for Endostar combined with a gemcitabine/cisplatin regimen in locally advanced or metastatic lung squamous cell carcinoma: a retrospective observational study [J]. Medicine, 2018, 97(32):e11822. doi:10.1097/MD.0000000000011822.
[8] 王聪,朱玲,万云焱,等. 重组人血管内皮抑制素不同给药途径联合顺铂对小鼠Lewis肺癌的疗效[J].山东大学学报(医学版), 2019, 57(5): 93-98. WANG Cong, ZHU Ling, WAN Yunyan, et al.Therapeutic effect of different administration ways of recombinant human endostatin combined with cisplatin on Lewis lung cancer xenografts in mice [J]. Journal of Shandong University(Health Sciences), 2019, 57(5): 93-98.
[9] Horsman MR, Vaupel P. Pathophysiological basis for the formation of the tumor microenvironment[J]. Front Oncol, 2016, 6: 66.doi: 10.3389/fonc.2016.00066.
[10] Chen X, Zhang H, Zhu H, et al. Endostatin combined with radiotherapy suppresses vasculogenic mimicry formation through inhibition of epithelial-mesenchymal transition in esophageal cancer[J]. TumourBiol, 2016, 37(4): 4679-4688.
[11] Potente M, Gerhardt H, Carmeliet P. Basic and therapeutic aspects of angiogenesis[J]. Cell, 2011, 146(6): 873-887.
[12] Ackermann M, Konerding MA. Vascular casting for the study of vascular morphogenesis[J]. Methods Mol Biol, 2015, 1214: 49-66.doi: 10.1007/978-1-4939-1462-3_5.
[13] Alahuhta I, Aikio M, Vayrynen O, et al. Endostatin induces proliferation of oral carcinoma cells but its effect on invasion is modified by the tumor microenvironment[J]. Exp Cell Res, 2015, 336(1): 130-140.
[14] Peng F, Xu Z, Wang J, et al. Recombinant human endostatin normalizes tumor vasculature and enhances radiation response in xenografted human nasopharyngeal carcinoma models[J]. PLoS One, 2012, 7(4): e34646.doi: 10.1371/journal.pone.0034646.
[15] Wu Y, Meitzler JL, Antony S, et al. Dual oxidase 2 and pancreatic adenocarcinoma: IFN-γ-mediated dual oxidase 2 overexpression results in H2O2-induced, ERK-associated up-regulation of HIF-1α and VEGF-A[J]. Oncotarget, 2016, 7(42): 68412-68433.
[16] Laug R, Fehrholz M, Schütze N, et al. IFN-γ and TNF-α synergize to inhibit CTGF expression in human lung endothelial cells[J]. PLoS One, 2012, 7(9): e45430.doi: 10.1371/journal.pone.0045430.
[17] Liu X, Nie W, Xie Q, et al. Endostatin reverses immunosuppression of the tumor microenvironment in lung carcinoma[J]. Oncol Lett, 2018, 15(2): 1874-1880.
[18] Jiang S, Wang G, Dong Y. Endostatin combined with chemotherapy in a pediatric osteosarcoma with pulmonary metastasis and malignant pleural effusion: a case report[J]. Medicine(Baltimore), 2017, 96(51): e9077.doi: 10.1097/MD.0000000000009077.
[19] Guset G, Costi S, Lazar E, et al. Expression of vascular endothelial growth factor(VEGF)and assessment of microvascular density with CD34 as prognostic markers for endometrial carcinoma[J]. Rom J MorpholEmbryol, 2010, 51(4): 677-682.
[20] Sakurai T, Kudo M. Signaling pathways governing tumor angiogenesis[J]. Oncology, 2011, Suppl 1: 24-29. doi:10.1159/000333256.
[21] Liu ZJ, Semenza GL, Zhang HF. Hypoxia-inducible factor 1 and breast cancer metastasis[J]. J Zhejiang Univ Sci B, 2015, 16(1): 32-43.
[22] Ji R C. Hypoxia and lymphangiogenesis in tumor microenvironment and metastasis[J]. Cancer Lett, 2014, 346(1): 6-16.
[1] 于德新 蔡跃红 马祥兴 张晓明 李传福. 肝细胞癌血管生成及其成熟度的临床意义[J]. 山东大学学报(医学版), 2209, 47(6): 51-54.
[2] 韩靖,贾春玲. 肺癌患者胸外手术前治疗牙周基础疾病对预防术后肺炎发生的效果评价[J]. 山东大学学报 (医学版), 2022, 60(9): 113-118.
[3] 高中霞,张铭,樊明德,谭晨阳,王梦迪,王超,樊跃飞,丁守銮,王成伟. 伽玛刀治疗81例肺癌脑转移瘤的疗效及预后因素[J]. 山东大学学报 (医学版), 2022, 60(8): 44-49.
[4] 秦静,杨飞,陈谦,夏涵岱,刘延国,王秀问. 晚期驱动基因阴性、PD-L1表达阴性非鳞非小细胞肺癌一线治疗方案的网状Meta分析[J]. 山东大学学报 (医学版), 2022, 60(7): 74-82.
[5] 王福立,孙银萍,秦杰,荣建胜. DC-CIK细胞联合EGFR-TKI治疗35例老年晚期EGFR突变肺癌的效果[J]. 山东大学学报 (医学版), 2022, 60(7): 110-117.
[6] 孙丽娜,杜晓晓,张红娟,孟金来. 人类白细胞抗原G调控蜕膜自然杀伤细胞促进滋养细胞侵袭[J]. 山东大学学报 (医学版), 2022, 60(6): 41-45.
[7] 陈兆波,方敏,薛浩然,刘春艳. 去泛素化酶USP35促进非小细胞肺癌细胞迁移和侵袭[J]. 山东大学学报 (医学版), 2022, 60(4): 30-37.
[8] 李鸿皓,于晶,陈亚丽,郭守刚. 20例NMOSD患者CD4+CD25+FoxP3+调节性T细胞数量和FoxP3 mRNA的表达水平[J]. 山东大学学报 (医学版), 2022, 60(4): 50-54.
[9] 于金明,颜薇薇,陈大卫. 肺癌放射免疫新实践[J]. 山东大学学报 (医学版), 2021, 59(9): 1-8.
[10] 曹义海. 血管生成在疾病治疗中的应用与展望[J]. 山东大学学报 (医学版), 2021, 59(9): 9-14.
[11] 张煜,唐兴,马海涛,蒋威. 荧光染色技术在胸腔镜肺段切除术中的价值[J]. 山东大学学报 (医学版), 2020, 58(12): 38-42.
[12] 张喜琴,祝守慧,刘宁,王玉,陈家帧,胡旭东. PEG-rhG-CSF对80例小细胞肺癌同步放化疗预防中性粒细胞减少的临床观察[J]. 山东大学学报 (医学版), 2020, 58(12): 43-46.
[13] 刘小璟,夏西燕,肖珂,陈文丹,庄学伟. 外泌体lncRNA OGFRP1在84例非小细胞肺癌中的表达及临床意义[J]. 山东大学学报 (医学版), 2020, 58(11): 71-75.
[14] 吕高超,蒋胜华,山凤莲,姜鲁宁. 以乳糜胸和纵隔占位为表现的淋巴瘤患者曲折诊治1例[J]. 山东大学学报 (医学版), 2019, 57(7): 117-121.
[15] 陈红艳,马园园,孙虎魁. 肺癌患者18F-FDG PET/CT SUVmax与程序性死亡受体-配体1表达相关性的Meta分析[J]. 山东大学学报 (医学版), 2019, 57(6): 81-86.
Full text



No Suggested Reading articles found!