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International Journal of Molecular Medicine
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September 2012 Volume 30 Issue 3

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Article

Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment

  • Authors:
    • Hong He
    • Ping Fan
    • Tao Yin
    • Qiaoling Chen
    • Huashan Shi
    • Sijia Liu
    • Haoyu Li
    • Qiuping  Jing
    • Yingying Yan
    • Hailong Zhang
    • Li Yang
    • Yanjun Wen
    • Yuhua Li
    • Ping Cheng
  • View Affiliations / Copyright

    Affiliations: State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan, P.R. China, School of Life Science, Sichuan University, Chengdu, Sichuan, P.R. China
  • Pages: 599-605
    |
    Published online on: June 12, 2012
       https://doi.org/10.3892/ijmm.2012.1027
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Abstract

Hepatocellular carcinoma (HCC) is a typical hypervascular tumor. Our previous studies have demonstrated that hepatitis B virus X protein (HBx) was able to inhibit the growth of HCC cells via inducing apoptosis and inhibiting tumor angiogenesis. Interleukin-12 (IL-12) is a disulfide-linked heterodimeric cytokine with potent immunostimulatory activity and anti-angiogenic properties. In this study, to further investigate the regulatory effect of IL-12 on HBx-mediated intervention of hepatoma microenvironment especially on intervention of neovessels and immune microenvironment, we constructed the recombinant adenovirus expressing HBx and mouse IL-12 named Ad-HBx-mIL-12. HBx-mIL-12 could effectively suppress tumor growth and induce apoptosis in vivo. Moreover, treatment with Ad-HBx-mIL-12 not only induced a massive accumulation of immune cells (CD8+ T leukocytes, macrophages and dendritic cells) in tumors in situ, also apparently reduced the number of angiogenic blood vessels within tumor tissues. These results suggest that HBx-mIL-12 can not only induce cell cycle arrest and apoptosis in HCC cells, but also effectively shift the tumor microenvironment from pro-oncogenic to antitumor through recruitment of immune cells and inhibiting stromal cell growth, such as vascular endothelial cells.
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1. 

RP BeasleyRocks along the road to the control of HBV and HCCAnn Epidemiol19231234200910.1016/j.annepidem.2009.01.01719344859

2. 

K OkudaHepatocellular carcinomaJ Hepatol32225237200010.1016/S0168-8278(00)80428-6

3. 

H TangN OishiS KanekoS MurakamiMolecular functions and biological roles of hepatitis B virus x proteinCancer Sci97977983200610.1111/j.1349-7006.2006.00299.x16984372

4. 

P ChengY LiL YangHepatitis B virus X protein (HBx) induces G2/M arrest and apoptosis through sustained activation of cyclin B1-CDK1 kinaseOncol Rep22110111072009

5. 

T TianKJ NanSH WangPTEN regulates angiogenesis and VEGF expression through phosphatase-dependent and -independent mechanisms in HepG2 cellsCarcinogenesis3112111219201010.1093/carcin/bgq08520430845

6. 

M FernandezD SemelaJ BruixI ColleM PinzaniJ BoschAngiogenesis in liver diseaseJ Hepatol50604620200910.1016/j.jhep.2008.12.011

7. 

L LiuY CaoC ChenSorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5Cancer Res661185111858200610.1158/0008-5472.CAN-06-137717178882

8. 

X ChenX LinJ ZhaoA tumor-selective biotherapy with prolonged impact on established metastases based on cytokine gene-engineered MSCsMol Ther16749756200810.1038/mt.2008.318362930

9. 

C GuiducciAP VicariS SangalettiG TrinchieriMP ColomboRedirecting in vivo elicited tumor infiltrating macrophages and dendritic cells towards tumor rejectionCancer Res6534373446200515833879

10. 

E ChunJ LeeHS CheongKY LeeTumor eradication by hepatitis B virus X antigen-specific CD8+ T cells in xenografted nude miceJ Immunol17011831190200310.4049/jimmunol.170.3.118312538674

11. 

Y LiP ChengY WenT lymphocyte responses against hepatitis B virus-related hepatocellular carcinoma induced by adenovirus vaccine encoding HBxInt J Mol Med268698762010

12. 

FX DingF WangYM LuMultiepitope peptide-loaded virus-like particles as a vaccine against hepatitis B virus-related hepatocellular carcinomaHepatology4914921502200910.1002/hep.2281619206147

13. 

YJ WangY HouH HuangGR LiuAP WhiteSL LiuTwo oral HBx vaccines delivered by live attenuated Salmonella: both eliciting effective anti-tumor immunityCancer Lett2636776200810.1016/j.canlet.2007.12.02218226855

14. 

A HombachC HeuserH AbkenSimultaneous targeting of IL2 and IL12 to Hodgkin’s lymphoma cells enhances activation of resting NK cells and tumor cell lysisInt J Cancer1152412472005

15. 

C HalinS RondiniF NilssonEnhancement of the antitumor activity of interleukin-12 by targeted delivery to neovasculatureNat Biotechnol20264269200210.1038/nbt0302-26411875427

16. 

LS PengML PenichetSL MorrisonA single-chain IL-12 IgG3 antibody fusion protein retains antibody specificity and IL-12 bioactivity and demonstrates antitumor activityJ Immunol1632502581999

17. 

JA HendrzakMJ BrundaAntitumor and antimetastatic activity of interleukin-12Curr Top Microbiol Immunol21365831996

18. 

G TrinchieriImmunobiology of interleukin-12Immunol Res17269278199810.1007/BF02786451

19. 

Y NasuCH BangmaGW HullCombination gene therapy with adenoviral vector-mediated HSV-tk+ GCV and IL-12 in an orthotopic mouse model for prostate cancerProstate Cancer Prostatic Dis44451200110.1038/sj.pcan.450049412497062

20. 

CM CouglinKE SalhangM WysockaInterleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesisJ Clin Invest10114411452199810.1172/JCI15559502787

21. 

BM PützerM HittWJ MullerInterleukin 12 and B7-1 co-stimulatory molecule expressed by an adenovirus vector act synergistically to facilitate tumor regressionProc Natl Acad Sci USA94108891089519979380730

22. 

JD BuiR UppaluriCS HsiehRD SchreiberComparative analysis of regulatory and effector T cells in progressively growing versus rejecting tumors of similar originsCancer Res6673017309200610.1158/0008-5472.CAN-06-055616849580

23. 

M KortylewskiP SwiderskiA HerrmannIn vivo delivery of siRNA to immune cells by conjugation to a TLR9 agonist enhances antitumor immune responsesNat Biotechnol27925932200910.1038/nbt.156419749770

24. 

M KujawskiM KortylewskiH LeeA HerrmannH KayH YuStat3 mediates myeloid cell-dependent tumor angiogenesis in miceJ Clin Invest11833673377200810.1172/JCI3521318776941

25. 

LM CoussensZ WerbInflammation and cancerNature420860867200210.1038/nature0132212490959

26. 

A MantovaniS SozzaniM LocatiP AllavenaA SicaMacrophage polarization: tumor-associated macrophages as a paradigm for polarized M2 mononuclear phagocytesTrends Immunol23549555200210.1016/S1471-4906(02)02302-512401408

27. 

PC RodriguezMS ErnstoffC HernandezArginase I-producing myeloid-derived suppressor cells in renal cell carcinoma are a subpopulation of activated granulocytesCancer Res6915531560200910.1158/0008-5472.CAN-08-192119201693

28. 

LA NorianPC RodriguezLA O’MaraTumor-infiltrating regulatory dendritic cells inhibit CD8+ T cell function via L-arginine metabolismCancer Res6930863094200910.1158/0008-5472.CAN-08-282619293186

29. 

SJ PiersmaES JordanovaMI van PoelgeestHigh number of intraepithelial CD8+ tumor-infiltrating lymphocytes is associated with the absence of lymph node metastases in patients with large early-stage cervical cancerCancer Res67354361200717210718

30. 

AG MenonGJ FleurenEA AlphenaarA basal membrane-like structure surrounding tumour nodules may prevent intraepithelial leucocyte infiltration in colorectal cancerCancer Immunol Immunother521211262003

31. 

E SatoSH OlsonJ AhnIntraepithelial CD8+ tumor-infiltrating lymphocytes and a high CD8+/regulatory T cell ratio are associated with favorable prognosis in ovarian cancerProc Natl Acad Sci USA10218538185432005

32. 

L ZhangJR Conejo-GarciaD KatsarosIntratumoral T cells, recurrence, and survival in epithelial ovarian cancerN Engl J Med348203213200310.1056/NEJMoa02017712529460

33. 

O SimmaE ZebedinN NeugebauerIdentification of an indispensable role for tyrosine kinase 2 in CTL-mediated tumor surveillanceCancer Res69203211200910.1158/0008-5472.CAN-08-170519118004

34. 

MN TorreroX XiaW HenkS YuS LiStat1 deficiency in the host enhances interleukin-12-mediated tumor regressionCancer Res6644614467200610.1158/0008-5472.CAN-05-355416618773

35. 

H KanzlerFJ BarratEM HesselRL CoffmanTherapeutic targeting of innate immunity with Toll-like receptor agonists and antagonistsNat Med13552559200710.1038/nm158917479101

36. 

W BarchetV WimmenauerM SchleeG HartmannAccessing the therapeutic potential of immunostimulatory nucleic acidsCurr Opin Immunol20389395200810.1016/j.coi.2008.07.00718652893

37. 

CS TannenbaumN WickerD ArmstrongCytokine and chemokine expression in tumors of mice receiving systemic therapy with IL-12J Immunol15669369919968543822

38. 

S AdrisE ChuluyanA BravoMice vaccination with interleukin 12-transduced colon cancer cells potentiates rejection of syngeneic non-organ-related tumor cellsCancer Res6066966703200011118055

39. 

CL NastalaHD EdingtonTG McKinneyRecombinant IL-12 administration induces tumor regression in association with IFN-gamma productionJ Immunol1531697170619947913943

40. 

AD LusterP LederIP-10, a -C-X-C- chemokine, elicits a potent thymus-dependent antitumor response in vivoJ Exp Med17810571065199310.1084/jem.178.3.10578350046

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Copy and paste a formatted citation
Spandidos Publications style
He H, Fan P, Yin T, Chen Q, Shi H, Liu S, Li H, Jing Q, Yan Y, Zhang H, Zhang H, et al: Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment. Int J Mol Med 30: 599-605, 2012.
APA
He, H., Fan, P., Yin, T., Chen, Q., Shi, H., Liu, S. ... Cheng, P. (2012). Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment. International Journal of Molecular Medicine, 30, 599-605. https://doi.org/10.3892/ijmm.2012.1027
MLA
He, H., Fan, P., Yin, T., Chen, Q., Shi, H., Liu, S., Li, H., Jing, Q., Yan, Y., Zhang, H., Yang, L., Wen, Y., Li, Y., Cheng, P."Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment". International Journal of Molecular Medicine 30.3 (2012): 599-605.
Chicago
He, H., Fan, P., Yin, T., Chen, Q., Shi, H., Liu, S., Li, H., Jing, Q., Yan, Y., Zhang, H., Yang, L., Wen, Y., Li, Y., Cheng, P."Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment". International Journal of Molecular Medicine 30, no. 3 (2012): 599-605. https://doi.org/10.3892/ijmm.2012.1027
Copy and paste a formatted citation
x
Spandidos Publications style
He H, Fan P, Yin T, Chen Q, Shi H, Liu S, Li H, Jing Q, Yan Y, Zhang H, Zhang H, et al: Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment. Int J Mol Med 30: 599-605, 2012.
APA
He, H., Fan, P., Yin, T., Chen, Q., Shi, H., Liu, S. ... Cheng, P. (2012). Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment. International Journal of Molecular Medicine, 30, 599-605. https://doi.org/10.3892/ijmm.2012.1027
MLA
He, H., Fan, P., Yin, T., Chen, Q., Shi, H., Liu, S., Li, H., Jing, Q., Yan, Y., Zhang, H., Yang, L., Wen, Y., Li, Y., Cheng, P."Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment". International Journal of Molecular Medicine 30.3 (2012): 599-605.
Chicago
He, H., Fan, P., Yin, T., Chen, Q., Shi, H., Liu, S., Li, H., Jing, Q., Yan, Y., Zhang, H., Yang, L., Wen, Y., Li, Y., Cheng, P."Local delivery of recombinant adenovirus expressing hepatitis B virus X protein and interleukin-12 results in antitumor effects via inhibition of hepatoma cell growth and intervention of tumor microenvironment". International Journal of Molecular Medicine 30, no. 3 (2012): 599-605. https://doi.org/10.3892/ijmm.2012.1027
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