Journal of Shandong University (Health Sciences) ›› 2020, Vol. 58 ›› Issue (1): 1-5.doi: 10.6040/j.issn.1671-7554.0.2019.1037

   

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

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

CLC Number: 

  • 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.
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