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Effect of Endostar combined with angiopoietin-2 inhibitor on malignant pleural effusion in mice

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Abstract

The present study was designed to investigate the synergetic effect of Endostar combined with an angiopoietin-2 specific inhibitor L1-10 on malignant pleural effusion (MPE) mouse model. A MPE mouse model was established by injecting Lewis lung carcinoma (LLC) cells into pleural cavity of C57BL/6 mice. The mice were randomly divided into four treatment groups: saline, Endostar, L1-10, and Endostar + L1-10. In the present study, we reported for the first time that Endostar combined with L1-10 had significant synergistic effects on the formation of MPE and tumor growth. Moreover, Endostar combined with L1-10 had additive effect on the attenuation of pleural inflammation, inhibition of tumor angiogenesis and pleural vascular hyperpermeability, which are central to the inhibition of MPE. Finally, these studies also found that Endostar combined with L1-10 could have complementary actions by reducing VEGF and IL-6 local release and downregulating VEGF expression in pleural tumors, which involved in the pathogenesis of MPE. Therefore, combined therapy with Endostar and L1-10 may be an encouraging strategy for the treatment of MPE.

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References

  1. Moschos C, Psallidas I, Kollintza A, Karabela S, Papapetropoulos A, Papiris S, et al. The angiopoietin/Tie2 axis mediates malignant pleural effusion formation. Neoplasia. 2009;11(3):298–304.

    CAS  PubMed Central  PubMed  Google Scholar 

  2. Bradshaw M, Mansfield A, Peikert T. The role of vascular endothelial growth factor in the pathogenesis, diagnosis and treatment of malignant pleural effusion. Curr Oncol Rep. 2013;15(3):207–16. doi:10.1007/s11912-013-0315-7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Zhang Y, Yu LK, Lu GJ, Xia N, Xie HY, Hu W, et al. Prognostic values of VEGF and endostatin with malignant pleural effusions in patients with lung cancer. Asian Pac J Cancer Prev. 2014;15(19):8435–40.

    Article  PubMed  Google Scholar 

  4. Kalomenidis I, Kollintza A, Sigala I, Papapetropoulos A, Papiris S, Light RW, et al. Angiopoietin-2 levels are elevated in exudative pleural effusions. Chest. 2006;129(5):1259–66. doi:10.1378/chest.129.5.1259.

    Article  CAS  PubMed  Google Scholar 

  5. Mulder SF, Boers-Sonderen MJ, van der Heijden HF, Vissers KC, Punt CJ, van Herpen CM. A phase II study of cediranib as palliative treatment in patients with symptomatic malignant ascites or pleural effusion. Target Oncol. 2014. doi:10.1007/s11523-014-0306-0.

    PubMed  Google Scholar 

  6. Dong XP, Xiao TH, Dong H, Jiang N, Zhao XG. Endostar combined with cisplatin inhibits tumor growth and lymphatic metastasis of lewis lung carcinoma xenografts in mice. Asian Pac J Cancer Prev. 2013;14(5):3079–83.

    Article  PubMed  Google Scholar 

  7. Ma X, Yao Y, Yuan D, Liu H, Wang S, Zhou C, et al. Recombinant human endostatin endostar suppresses angiogenesis and lymphangiogenesis of malignant pleural effusion in mice. PLoS One. 2012;7(12):e53449. doi:10.1371/journal.pone.0053449.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Chen X, Liu Y, Yin Y, Jin S, Ping G, Roe OD, et al. Recombinant human endostatin (endostar) decreased recurrent ascites, pleural fluid and ascitic VEGF in a case of advanced mesothelioma. J Chemother. 2012;24(4):231–6. doi:10.1179/1973947812Y.0000000023.

    Article  PubMed  Google Scholar 

  9. Jiang ZY, Qin SK, Yin XJ, Chen YL, Zhu L. Synergistic effects of Endostar combined with beta-elemene on malignant ascites in a mouse model. Exp Ther Med. 2012;4(2):277–84. doi:10.3892/etm.2012.583.

    CAS  PubMed Central  PubMed  Google Scholar 

  10. Kienast Y, Klein C, Scheuer W, Raemsch R, Lorenzon E, Bernicke D, et al. Ang-2-VEGF-A CrossMab, a novel bispecific human IgG1 antibody blocking VEGF-A and Ang-2 functions simultaneously, mediates potent antitumor, antiangiogenic, and antimetastatic efficacy. Clin Cancer Res. 2013;19(24):6730–40. doi:10.1158/1078-0432.CCR-13-0081.

    Article  CAS  PubMed  Google Scholar 

  11. Economidou F, Margaritopoulos G, Antoniou KM, Siafakas NM. The angiogenetic pathway in malignant pleural effusions: pathogenetic and therapeutic implications. Exp Ther Med. 2010;1(1):3–7. doi:10.3892/etm_00000001.

    CAS  PubMed Central  PubMed  Google Scholar 

  12. Hashizume H, Falcon BL, Kuroda T, Baluk P, Coxon A, Yu D, et al. Complementary actions of inhibitors of angiopoietin-2 and VEGF on tumor angiogenesis and growth. Cancer Res. 2010;70(6):2213–23. doi:10.1158/0008-5472.CAN-09-1977.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Stathopoulos GT, Kollintza A, Moschos C, Psallidas I, Sherrill TP, Pitsinos EN, et al. Tumor necrosis factor-alpha promotes malignant pleural effusion. Cancer Res. 2007;67(20):9825–34. doi:10.1158/0008-5472.CAN-07-1064.

    Article  CAS  PubMed  Google Scholar 

  14. Stathopoulos GT, Psallidas I, Moustaki A, Moschos C, Kollintza A, Karabela S, et al. A central role for tumor-derived monocyte chemoattractant protein-1 in malignant pleural effusion. J Natl Cancer Inst. 2008;100(20):1464–76. doi:10.1093/jnci/djn325.

    Article  CAS  PubMed  Google Scholar 

  15. Fang F, Chen P, Wu X, Yang L, Yang X, Xi ZX, et al. Therapeutic effects of recombinant human endostatin adenovirus in a mouse model of malignant pleural effusion. J Cancer Res Clin Oncol. 2009;135(9):1149–57. doi:10.1007/s00432-009-0555-y.

    Article  CAS  PubMed  Google Scholar 

  16. Shibuya M. Vascular endothelial growth factor-dependent and -independent regulation of angiogenesis. BMB Rep. 2008;41(4):278–86.

    Article  CAS  PubMed  Google Scholar 

  17. Yeh HH, Chang WT, Lu KC, Lai WW, Liu HS, Su WC. Upregulation of tissue factor by activated Stat3 contributes to malignant pleural effusion generation via enhancing tumor metastasis and vascular permeability in lung adenocarcinoma. PLoS One. 2013;8(9):e75287. doi:10.1371/journal.pone.0075287.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Mancuso MR, Davis R, Norberg SM, O’Brien S, Sennino B, Nakahara T, et al. Rapid vascular regrowth in tumors after reversal of VEGF inhibition. J Clin Invest. 2006;116(10):2610–21. doi:10.1172/JCI24612.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  19. Narita Y. Drug review: safety and efficacy of bevacizumab for glioblastoma and other brain tumors. Jpn J Clin Oncol. 2013;43(6):587–95. doi:10.1093/jjco/hyt051.

    Article  PubMed  Google Scholar 

  20. Bagri A, Berry L, Gunter B, Singh M, Kasman I, Damico LA, et al. Effects of anti-VEGF treatment duration on tumor growth, tumor regrowth, and treatment efficacy. Clin Cancer Res. 2010;16(15):3887–900. doi:10.1158/1078-0432.CCR-09-3100.

    Article  CAS  PubMed  Google Scholar 

  21. Paez-Ribes M, Allen E, Hudock J, Takeda T, Okuyama H, Vinals F, et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell. 2009;15(3):220–31. doi:10.1016/j.ccr.2009.01.027.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. Chae SS, Kamoun WS, Farrar CT, Kirkpatrick ND, Niemeyer E, de Graaf AM, et al. Angiopoietin-2 interferes with anti-VEGFR2-induced vessel normalization and survival benefit in mice bearing gliomas. Clin Cancer Res. 2010;16(14):3618–27. doi:10.1158/1078-0432.CCR-09-3073.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Rigamonti N, Kadioglu E, Keklikoglou I, Wyser Rmili C, Leow CC, De Palma M. Role of angiopoietin-2 in adaptive tumor resistance to VEGF signaling blockade. Cell Rep. 2014;8(3):696–706. doi:10.1016/j.celrep.2014.06.059.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This work was supported by a Grant from International Medical Exchange Fund of China (CIMF-F-H001-104).

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Authors and Affiliations

  1. Department of Respiratory Medicine Center, Nanjing Chest Hospital, 215 Guangzhou Road, Nanjing, 210029, People’s Republic of China

    Shen-Cun Fang, Hai-Tao Zhang, Cai-Ying Wang & Ying-Ming Zhang

  2. Department of Pathology, Nanjing Chest Hospital, 215 Guangzhou Road, Nanjing, 210029, People’s Republic of China

    Hui-Di Hu

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  1. Shen-Cun Fang
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  2. Hai-Tao Zhang
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Correspondence to Ying-Ming Zhang.

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Shen-Cun Fang and Hai-Tao Zhang have contributed equally to this work.

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Fang, SC., Zhang, HT., Hu, HD. et al. Effect of Endostar combined with angiopoietin-2 inhibitor on malignant pleural effusion in mice. Med Oncol 32, 410 (2015). https://doi.org/10.1007/s12032-014-0410-0

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  • DOI: https://doi.org/10.1007/s12032-014-0410-0

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