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 •
徐鹏飞1,朱玲1,万云焱1,姚周虹1,李德志1,王聪2,翟聪聪3,李文4,林殿杰1
XU Pengfei1, ZHU Ling1, WAN Yunyan1, YAO Zhouhong1, LI Dezhi1, WANG Cong2, ZHAI Congcong3, LI Wen4, LIN Dianjie1
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。
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[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. |
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