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Neamine inhibits growth of pancreatic cancer cells In Vitro and In Vivo

  • Ya-ping Liu (刘亚萍)
  • Yan-li Wu (吴艳丽)
  • Xiao-yan Zhang (章晓燕)
  • Guo-fu Hu (胡国富)
  • Yun-xia Wu (吴云霞)Email author
Article

Summary

Neamine, a non-toxic derivative of neomycin, has recently been shown to have antitumor activities in various types of cancers. However, its effect on pancreatic cancer is still unknown. The study aimed to investigate its antitumor activity on pancreatic cancer and the underlying mechanisms. MTT assay was used to observe the effect of neamine on angiogenin (ANG)-induced AsPC-1 cell proliferation. Tissue microassay and immunofluorescence staining were used to detect the expression of ANG and its nuclear translocation, respectively. Tumor xenografts were established by subcutaneous inoculation of AsPC-1 pancreatic cancer cells into the right flanks of nude mice, and neamine was injected subcutaneously. Immunohistochemistry was done to observe the expression of ANG, CD31 and Ki-67 in tumor xenografts. It was found that neamine blocked the nuclear translocation of ANG effectively and inhibited ANG-induced AsPC-1 cell proliferation in a dose-dependent manner. Neamine had anti-tumor effects on AsPC-1 xenograft models. Consistently, neamine reduced the expression levels of ANG, Ki-67 and CD31 in tumor xenografts. It was concluded that neamine may be a promising agent for treatment of pancreatic cancer.

Key words

neamine angiogenin pancreatic cancer cell proliferation angiogenesis 

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References

  1. 1.
    Vincent A, Herman J, Schulick R, et al. Pancreatic cancer. Lancet, 2011,378(9791):607–620PubMedCentralCrossRefPubMedGoogle Scholar
  2. 2.
    Siegel R, Ma J, Zou Z, et al. Cancer statistics. CA cancer J Clin, 2014,64(1):9–29CrossRefPubMedGoogle Scholar
  3. 3.
    Liu SX, Xia ZS, Zhong YQ. Genetic therapy in pancreatic cancer. World J Gastroenterol, 2014,20(37): 13343–13368PubMedCentralCrossRefPubMedGoogle Scholar
  4. 4.
    Burris H, Storniolo A. Assessing clinical benefit in the treatment of pancreas cancer: gemcitabine compared to 5-fluorouracil. Eur J Cancer, 1997,33(suppl): S18–S22CrossRefPubMedGoogle Scholar
  5. 5.
    Seo Y, Baba H, Fukuda T, et al. High expression of vascular endothelial growth factor is associated with liver metastasis and a poor prognosis for patients with ductal pancreatic adenocarcinoma. Cancer, 2000,88(10): 2239–2245CrossRefPubMedGoogle Scholar
  6. 6.
    Fujimoto K, Hosotani R, Wada M, et al. Expression of two angiogenic factors, vascular endothelial growth factor and platelet-derived endothelial cell growth factor in human pancreatic cancer, and its relationship to angiogenesis. Eur J Cancer, 1998,34(9):1439–1447CrossRefPubMedGoogle Scholar
  7. 7.
    Wang H, Chen Q. Expression and significance of cyclooxygenase-2 in human pancreatic carcinomas. Chin Ger J Clin Oncol, 2005,22(2):121–123CrossRefGoogle Scholar
  8. 8.
    Fett JW, Strydom DJ, Lobb RR, et al. Isolation and characterization of angiogenin, an angiogenic protein from human carcinoma cells. Biochemistry, 1985,24(20): 5480–5486CrossRefPubMedGoogle Scholar
  9. 9.
    Li R, Riordan JF, Hu G. Nuclear translocation of human angiogenin in cultured human umbilical artery endothelial cells is microtubule and lysosome independent. Biochem Biophys Res Commun, 1997,238 (238):305–312CrossRefPubMedGoogle Scholar
  10. 10.
    Moroianu J, Riordan JF. Nuclear translocation of angiogenin in proliferating endothelial cells is essential to its angiogenic activity. Proc Natl Acad Sci USA, 1994,91(5):1677–1681PubMedCentralCrossRefPubMedGoogle Scholar
  11. 11.
    Kishimoto K, Liu S, Tsuji T, et al. Endogenous angiogenin in endothelial cells is a general requirement for cell proliferation and angiogenesis. Oncogene, 2005, 24(3):445–456CrossRefPubMedGoogle Scholar
  12. 12.
    Bottero V, Sadagopan S, Johnson KE, et al. Kaposi's sarcoma-associated herpesvirus-positive primary effusion lymphoma tumor formation in NOD/SCID mice is inhibited by neomycin and neamine blocking angiogenin's nuclear translocation. J Virol, 2013,87(21):11806–11820PubMedCentralCrossRefPubMedGoogle Scholar
  13. 13.
    Shimoyama S, Gansauge F, Gansauge S, et al. Increased angiogenin expression in pancreatic cancer is related to cancer aggressiveness. Cancer Res, 1996,56(12):2703–2706PubMedGoogle Scholar
  14. 14.
    Olson KA, Fett JW, French TC, et al. Angiogenin antagonists prevent tumor growth in vivo. Proc Natl Acad Sci USA, 1995,92(2):442–446PubMedCentralCrossRefPubMedGoogle Scholar
  15. 15.
    Olson KA, French TC, Vallee BL, et al. A monoclonal antibody to human angiogenin suppresses tumor growth in athymic mice. Cancer Res, 1994,54(17): 4576–4579PubMedGoogle Scholar
  16. 16.
    Olson KA, Byers HR, Key ME, et al. Prevention of human prostate tumor metastasis in athymic mice by antisense targeting of human angiogenin. Clin Cancer Res, 2001,7(11):3598–3605PubMedGoogle Scholar
  17. 17.
    Sadagopan S, Sharma-Walia N, Veettil MV, et al. Kaposi's sarcoma-associated herpesvirus upregulates angiogenin during infection of human dermal microvascular endothelial cells, which induces 45S rRNA synthesis, antiapoptosis, cell proliferation, migration, and angiogenesis. J Virol, 2009,83(7): 3342–3364PubMedCentralCrossRefPubMedGoogle Scholar
  18. 18.
    Hu GF. Neomycin inhibits angiogenin-induced angiogenesis. Proc Natl Acad Sci USA, 1998,95:9791–9795PubMedCentralCrossRefPubMedGoogle Scholar
  19. 19.
    Williams P, Bennett D, Gleason C, et al. Correlation between renal membrane binding and nephrotoxicity of aminoglycosides. Antimicrob Agents Chemother, 1987,31(4):570–574PubMedCentralCrossRefPubMedGoogle Scholar
  20. 20.
    Zhao J, Wang YC, Yang LY, et al. Neamine inhibits cell proliferation, migration, and invasion in H7402 human hepatoma cells. Saudi Med J, 2010,31(12):1309–1314PubMedGoogle Scholar
  21. 21.
    Kishimoto K, Yoshida S, Ibaragi S, et al. Neamine inhibits oral cancer progression by suppressing angiogenin-mediated angiogenesis and cancer cell proliferation. Anticancer Res, 2014,34(5):2113–2121PubMedGoogle Scholar
  22. 22.
    Yuan Y, Wang F, Liu XH, et al. Angiogenin is involved in lung adenocarcinoma cell proliferation and angiogenesis. Lung Cancer, 2009,66(1):28–36CrossRefPubMedGoogle Scholar
  23. 23.
    Hirukawa S, Olson KA, Tsuji T, et al. Neamine inhibits xenografic human tumor growth and angiogenesis in athymic mice. Clin Cancer Res, 2005, 11(24 Pt 1): 8745–8752CrossRefPubMedGoogle Scholar
  24. 24.
    Ibaragi S, Yoshioka N, Li S, et al. Neamine inhibits prostate cancer growth by suppressing angiogeninmediated rRNA transcription. Clin Cancer Res, 2009, 15(6):1981–1988PubMedCentralCrossRefPubMedGoogle Scholar
  25. 25.
    Yaping Liu, Xiaoyan Zhang, Songlin An, et al. Pharmacokinetics of neamine in rats and anti-cervical cancer activity in vitro and in vivo. Cancer Chemother Pharmacol, 2015, 75(3):465–474CrossRefGoogle Scholar
  26. 26.
    Liu YP, Hu GF, Wu YX. Neamine is preferential as an anti-prostate cancer reagent by inhibiting cell proliferation and angiogenesis with lower toxicity than cis-platinum. Oncol Lett, 2015,10(1):137–142PubMedCentralPubMedGoogle Scholar
  27. 27.
    Deng SR, Li J, Zhang ZQ, et al. DS147 improves pregnancy in mice with embryo implantation dysfunction induced by controlled ovarian stimulation. J Huazhong Univ Sci Technolog Med Sci, 2013,33(4):573–580CrossRefPubMedGoogle Scholar
  28. 28.
    Saif MW. Anti-angiogenesis therapy in pancreatic carcinoma. Jop, 2006,7(2):163–173PubMedGoogle Scholar
  29. 29.
    Tsuji T, Sun Y, Kishimoto K, et al. Angiogenin is translocated to the nucleus of HeLa cells and is involved in ribosomal RNA transcription and cell proliferation. Cancer Res, 2005,65(4):1352–1360CrossRefPubMedGoogle Scholar
  30. 30.
    Sathish S, Mohanan VV, Nitika P, et al. Kaposi's sarcoma-associated herpesvirus-induced angiogenin plays roles in latency via the phospholipase C gamma pathway: blocking angiogenin inhibits latent gene expression and induces the lytic cycle. J Virol, 2011,85(6):2666–2685CrossRefGoogle Scholar

Copyright information

© Huazhong University of Science and Technology and Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Ya-ping Liu (刘亚萍)
    • 1
  • Yan-li Wu (吴艳丽)
    • 1
  • Xiao-yan Zhang (章晓燕)
    • 1
  • Guo-fu Hu (胡国富)
    • 2
  • Yun-xia Wu (吴云霞)
    • 1
    Email author
  1. 1.School of Pharmacy, Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina
  2. 2.Molecular Oncology Research InstituteTufts Medical CenterBostonUSA

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