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

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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.

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References

  1. Vincent A, Herman J, Schulick R, et al. Pancreatic cancer. Lancet, 2011,378(9791):607–620

    Article  PubMed Central  PubMed  Google Scholar 

  2. Siegel R, Ma J, Zou Z, et al. Cancer statistics. CA cancer J Clin, 2014,64(1):9–29

    Article  PubMed  Google Scholar 

  3. Liu SX, Xia ZS, Zhong YQ. Genetic therapy in pancreatic cancer. World J Gastroenterol, 2014,20(37): 13343–13368

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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–S22

    Article  CAS  PubMed  Google Scholar 

  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): 2239–2245

    Article  CAS  PubMed  Google Scholar 

  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):1439–1447

    Article  CAS  PubMed  Google Scholar 

  7. Wang H, Chen Q. Expression and significance of cyclooxygenase-2 in human pancreatic carcinomas. Chin Ger J Clin Oncol, 2005,22(2):121–123

    Article  Google Scholar 

  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): 5480–5486

    Article  CAS  PubMed  Google Scholar 

  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):305–312

    Article  CAS  PubMed  Google Scholar 

  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):1677–1681

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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):445–456

    Article  CAS  PubMed  Google Scholar 

  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):11806–11820

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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):2703–2706

    CAS  PubMed  Google Scholar 

  14. Olson KA, Fett JW, French TC, et al. Angiogenin antagonists prevent tumor growth in vivo. Proc Natl Acad Sci USA, 1995,92(2):442–446

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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): 4576–4579

    CAS  PubMed  Google Scholar 

  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):3598–3605

    CAS  PubMed  Google Scholar 

  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): 3342–3364

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Hu GF. Neomycin inhibits angiogenin-induced angiogenesis. Proc Natl Acad Sci USA, 1998,95:9791–9795

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. Williams P, Bennett D, Gleason C, et al. Correlation between renal membrane binding and nephrotoxicity of aminoglycosides. Antimicrob Agents Chemother, 1987,31(4):570–574

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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):1309–1314

    PubMed  Google Scholar 

  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):2113–2121

    CAS  PubMed  Google Scholar 

  22. Yuan Y, Wang F, Liu XH, et al. Angiogenin is involved in lung adenocarcinoma cell proliferation and angiogenesis. Lung Cancer, 2009,66(1):28–36

    Article  PubMed  Google Scholar 

  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): 8745–8752

    Article  CAS  PubMed  Google Scholar 

  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):1981–1988

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  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):465–474

    Article  Google Scholar 

  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):137–142

    PubMed Central  PubMed  Google Scholar 

  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):573–580

    Article  CAS  PubMed  Google Scholar 

  28. Saif MW. Anti-angiogenesis therapy in pancreatic carcinoma. Jop, 2006,7(2):163–173

    PubMed  Google Scholar 

  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):1352–1360

    Article  CAS  PubMed  Google Scholar 

  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):2666–2685

    Article  Google Scholar 

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Correspondence to Yun-xia Wu  (吴云霞).

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This work was supported by grants from the National Major Special Project of the Ministry of Science and Technology of China (No. 2012ZX09103101047), the National Natural Science Foundation of China (No. 81373873) and the Special Fund for Basic Scientific Research of Central College of China (No. 2014QN129).

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Liu, Yp., Wu, Yl., Zhang, Xy. et al. Neamine inhibits growth of pancreatic cancer cells In Vitro and In Vivo . J. Huazhong Univ. Sci. Technol. [Med. Sci.] 36, 82–87 (2016). https://doi.org/10.1007/s11596-016-1546-2

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  • DOI: https://doi.org/10.1007/s11596-016-1546-2

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