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Inhibition of human lung adenocarcinoma growth using survivint34a by low-dose systematic administration

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Abstract

Anti-apoptosis plays an important role in tumour formation and development. Survivin is a member of the inhibitor of apoptosis (IAP) family, which is a target for anti-cancer drug exploitation was replaced as development. We investigated the role of the homo dominant-negative mutant Survivin-T34A in suppressing human lung adenocarcinomas (A549). The anti-tumour activity of HSurvivinT34A plasmid was evaluated in the A549 cell line and nude mice bearing A549 subcutaneous tumours. Low-dose systemic administration was continuously used. The HSurvivinT34A plasmid (5 µg/one) complexed with a cationic liposome (DOTAP/Chol) significantly inhibited tumour growth in our model. We observed microvessel density degradation by CD31 immunohistochemistry and apoptotic cell increase by TUNEL assay, PI staining and flow cytometric analysis in the treated group. The present findings suggest that the HSurvivinT34A plasmid complexed with a cationic liposome may provide an effective approach to inhibit the growth of human lung adenocarcinomas in vitro and in vivo.

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Abbreviations

ANOVA:

analysis of variance

FBS:

foetal bovine serum

H&E:

haematoxylin and eosin

IAP:

inhibitor of apoptosis

MVD:

microvessel density

NSCLC:

non-small cell lung cancer

PCR:

polymerase chain reaction

PI:

propidium iodine

P-S:

penicillin/streptomycin

TAL:

Tachypleus amebocyte lysate

TUNEL:

terminal eoxynucleotidyltransferase-mediated dUTP nick-end labelling

VEGF:

vascular endothelial growth factor

References

  • Altieri D C 2001 The molecular basis and potential role of survivin in cancer diagnosis and therapy; Trends. Mol. Med. 7 542–547

    Article  CAS  PubMed  Google Scholar 

  • Altieri D C and Marchisio C 1999 Survivin apoptosis: an interloper between cell death and cell proliferation in cancer; Lab. Invest. 79 1327–1333

    CAS  PubMed  Google Scholar 

  • Blanc-Brude O P, Mesri M, Wall N R, Plescia J, Dohi T and Altieri D C 2003 Therapeutic targeting of the survivin pathway in cancer: initiation of mitochondrial apoptosis and suppression of tumor-associated angiogenesis; Clin. Cancer Res. 9 2683–2692

    CAS  PubMed  Google Scholar 

  • Bo L, Yi M, Carolyn C, Fenghua Z, Sylke S, Jiahui T, Jim P, Jun C et al. 2004 Survivin as a therapeutic target for radiation sensitization in lung cancer; Cancer Res. 64 2840–2845

    Article  Google Scholar 

  • Branko Z 2007 Report 2007 12th World Conference on Lung Cancer. Seoul, Korea.

  • Chakravarti A, Noll E, Black P M, Finkelstein D F, Finkelstein D M, Dyson N J and Loeffler J S 2002 Quantitatively determined survivin expression levels are of prognostic value in human gliomas; J. Clin. Oncol. 20 1063–1068

    Article  CAS  PubMed  Google Scholar 

  • Connor D S, Grossman G, Plescia J, Li F, Zhang H, Villa A, Tognin S, Marchisio P C et al. 2000 Regulation of apoptosis at cell division by p34cdc2 phosphorylation of survivin; Proc. Natl. Acad. Sci. USA 97 13103–13107

    Article  Google Scholar 

  • Connor D S, Schechner J S, Adida C, Mesri M, Rothermel A L, Li F, Nath A K, Pober J S et al. 2000 Control of apoptosis during angiogenesis by survivin expression in endothelial cells; Am. J. Pathol. 156 393–398

    Google Scholar 

  • Connor D S, Wall N R, Porter A C G and Altieri D C 2002 A p34cdc2 survival checkpoint in cancer; Cancer Cell 2 43–54

    Article  Google Scholar 

  • Deveraux Q L and Reed J C 1999 IAP family proteins: suppressors of apoptosis; Genes. Dev. 13 239–252

    Article  CAS  PubMed  Google Scholar 

  • Du C, Fang M, Li Y, Li L and Wang X 2000 Smac, a mitochondrial protein that promotes cytochrome c-dependent caspase activation by eliminating IAP inhibition; Cell 102 33–42

    Article  CAS  PubMed  Google Scholar 

  • Grossman D, Kim P J, Schechner J S and Altieri D C 2001 Inhibition of melanoma tumor growth in vivo by survivin targeting; Proc. Natl. Acad. Sci. USA 98 635–640

    Article  CAS  PubMed  Google Scholar 

  • Grossman D, McNiff J M, Li F and Altieri D C 1999 Expression and targeting of the apoptosis inhibitor, survivin, in human melanoma; J. Invest. Dermatol. 113 1076–1081

    Article  CAS  PubMed  Google Scholar 

  • Harfouche R, Hassessian H M, Guo Y, Faivre V, Srikant C B, Yancopoulos G D and Hussain S N 2002 Mechanisms which mediate the antiapoptotic effects of angiopoietin-1 on endothelial cells; Microvasc. Res. 64 135–147

    Article  CAS  PubMed  Google Scholar 

  • Ito I, Began G, Mohiuddin I, Saeki T, Saito Y, Branch C D, Vaporciyan A, Stephens L C et al. 2003 Increased uptake of liposome-DNA complexes by lung metastases following intravenous administration; Mol. Ther. 7 409–418

    Article  CAS  PubMed  Google Scholar 

  • Jiang G, Li J, Zeng Z and Xian L 2006 Lentivirus-mediated gene therapy by suppressing survivin in BALB/c nude mice bearing oral squamous cell carcinoma; Cancer Biol. Ther. 5 435–440

    Article  CAS  PubMed  Google Scholar 

  • Kanwar J R, Shen W P, Kanwar R K, Berg R W and Krissansen G W 2001 Effects of survivin antagonists on growth of established tumors and B7-1 immunogene therapy; J. Natl. Cancer Inst. 93 1541–1552

    Article  CAS  PubMed  Google Scholar 

  • Kennedy S M, Driscoll L, Purcell R, Fitz-Simons N, McDermott E W, Hill A D, Higgins N J, Parkinson M et al. 2003 Prognostic importance of survivin in breast cancer; Br. J. Cancer 88 1077–1083

    Article  CAS  PubMed  Google Scholar 

  • Lu B, Gonzalez A, Massion P P, Shyr Y, Shaktour B, Carbone D P and Hallahan D E 2004 Nuclear survivin as a biomarker for nonsmall-cell lung cancer; Br. J. Cancer 91 537–540

    Article  CAS  PubMed  Google Scholar 

  • Mehdi M, Nathan R, Jia L, Richard W. Kim and Dario C 2001 Cancer gene therapy using a survivin mutant adenovirus; J. Clin. Invest. 108 981–990

    Google Scholar 

  • Mesri M, Morales-Ruiz M, Ackermann E J, Bennett C F, Pober J S, Sessa W C and Altieri D C 2001 Suppression of vascular endothelial growth factor-mediated endothelial cell protection by survivin targeting; Am. J. Pathol. 158 1757–1765

    CAS  PubMed  Google Scholar 

  • Mohamed S, Yasufuku K, Nakajima T, Hiroshima K, Chiyo M, Sekine Y, Shibuya K, Agamy G et al. 2009 Nuclear survivin in pN2 nonsmall cell lung cancer: prognostic and clinical implications; Eur. Respir. 33 127–133

    Article  CAS  Google Scholar 

  • Muzio L, Staibano S, Pannone G, Mignogna M D, Mariggio A, Salvatore G, Chieffi P, Tramontano D et al. 2001 Expression of the apoptosis inhibitor survivin in aggressive squamous cell carcinoma; Exp. Mol. Pathol. 70 249–254

    Article  PubMed  Google Scholar 

  • Papapetropoulos A, Fulton D, Mahboubi K, Kalb R G, Connor D S, Li F, Altieri D C and Sessa W C 2000 Angiopoietin-1 inhibits endothelial cell apoptosis via the Akt/survivin pathway; J. Biol. Chem. 275 9102–9105

    Article  CAS  PubMed  Google Scholar 

  • Peng X C, Yang L, Yang L P, Mao Y Q, Yang H S, Liu J Y, Zhang D M, Chen L J et al. 2008 Efficient inhibition of murine breast cancer growth and metastasis by gene transferred mouse survivin Thr34→Ala mutant; J. Exp. Clin. Cancer Res. 27 46–59

    Article  CAS  PubMed  Google Scholar 

  • Pennati M, Colella G, Folini M, Citti L, Daidone M G and Zaffaroni N 2002 Ribozyme-mediated attenuation of survivin expression sensitizes human melanoma cells to cisplatin-induced apoptosis; J. Clin. Invest. 109 285–286

    CAS  PubMed  Google Scholar 

  • Pisarev V, Yu B, Salup R, Sherman S and Gabrilovich D I 2003 Fulllength dominant-negative survivin for cancer immunotherapy; Clin. Cancer Res. 9 6523–6533

    CAS  PubMed  Google Scholar 

  • Ramesh R, Saeki T, Templeton N S, Ji L, Stephens L C, Ito I, Wilson D R, Wu Z et al. 2001 Successful treatment of primary and disseminated human lung cancers by systemic delivery of tumor suppressor genes using an improved liposome vector; Mol. Ther. 22 11–16

    Google Scholar 

  • Reed J C 1999 Dysregulation of apoptosis in cancer; J. Clin. Oncol. 17 2941–2953

    CAS  PubMed  Google Scholar 

  • Robert A, Olie A, Paula S, Bettina B, Sian H L, Doriano F, Rolf A and Stahel U 2000 A Novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy; Cancer Res. 60 2805–2809

    Google Scholar 

  • Rudin C M and Thompson C B 1997 Apoptosis and disease: regulation and clinical relevance of programmed cell death; Annu. Rev. Med. 48 267–281

    Article  CAS  PubMed  Google Scholar 

  • Shen C X, Liu W J, Andreas K B and Sven N R 2009 Pro-apoptosis and anti-proliferation effects of a recombinant dominantnegative survivin-t34a in human cancer cells; Anticancer Res. 29 1423–1428

    CAS  PubMed  Google Scholar 

  • Shi Y 2002 Mechanisms of caspase activation and inhibition during apoptosis; Mol. Cell. 9 459–470

    Article  CAS  PubMed  Google Scholar 

  • Thurston G, Mclean J W, Rizen M, Baluk P, Haskell A, Murphy T J, Hanahan D and McDonald D M 1998 Cationic liposome target angiogenic endothelial cells in tumors and chronic inflammation in mice; J. Clin. Invest. 101 1401–1413

    Article  CAS  PubMed  Google Scholar 

  • Tsuruma T, Hata F, Torigoe T, Furuhata T, Idenoue S, Kurotaki T, Yamamoto M, Yagihashi A et al. 2004 Phase I clinical study of antiapoptosis protein, surviving derived peptide vaccine therapy for patients with advanced or recurrent colorectal cancer; J. Transl. Med. 2 19–30

    Article  PubMed  Google Scholar 

  • Verdecia M A, Huang H, Dutil E, Kaiser D A, Hunter T and Noel J P 2000 Structure of the human anti-apoptotic protein survivin reveals a dimeric arrangement; Nat. Struct. Biol. 7 602–608

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Chunting Wang.

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These authors contributed equally to this research.

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Shan, Y., Wang, C., Yang, L. et al. Inhibition of human lung adenocarcinoma growth using survivint34a by low-dose systematic administration. J Biosci 35, 209–216 (2010). https://doi.org/10.1007/s12038-010-0025-3

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  • DOI: https://doi.org/10.1007/s12038-010-0025-3

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