Skip to main content

Advertisement

Log in

The efficacy of combination therapy using adeno-associated virus-mediated co-expression of apoptin and interleukin-24 on hepatocellular carcinoma

  • Research Article
  • Published:
Tumor Biology

Abstract

Multigene-based combination therapy is an effective practice in cancer gene therapy. Apoptin is a chicken anemia virus-derived, p53-independent, Bcl-2-insensitive apoptotic protein with the ability to specifically induce apoptosis in various human tumor cells. Interleukin-24 (IL-24) displays ubiquitous antitumor property and tumor-specific killing activity. Adeno-associated virus (AAV) is a promising gene delivery vehicle due to its advantage of low pathogenicity and long-term gene expression. In this study, we assessed the efficacy of combination therapy using AAV-mediated co-expression of apoptin and interleukin-24 on hepatocellular carcinoma in vitro and in vivo. Our results showed that AAV-mediated co-expression of IL-24 and apoptin significantly suppressed the growth and induced the apoptosis of HepG2 cells in vitro. Furthermore, AAV-mediated combined treatment of IL-24 and apoptin significantly suppressed tumor growth and induced apoptosis of tumor cells in xenograft nude mice. These data suggest that AAV vectors that co-express apoptin and IL-24 have great potential in cancer gene therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Parkin DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin. 2005;55:74–108.

    Article  PubMed  Google Scholar 

  2. Roberts LR. Sorafenib in liver cancer—just the beginning. N Engl J Med. 2008;359:420–2.

    Article  CAS  PubMed  Google Scholar 

  3. Roayaie S, Blume IN, Thung SN, et al. A system of classifying microvascular invasion to predict outcome after resection in patients with hepatocellular carcinoma. Gastroenterology. 2009;137:850–5.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Newell P, Villanueva A, Llovet JM. Molecular targeted therapies in hepatocellular carcinoma: from pre-clinical models to clinical trials. J Hepatol. 2008;49:1–5.

    Article  CAS  PubMed  Google Scholar 

  5. Yang CL, Jiang FQ, Xu F, Jiang GX. ADAM10 overexpression confers resistance to doxorubicin-induced apoptosis in hepatocellular carcinoma. Tumour Biol. 2012;33:1535–41.

    Article  CAS  PubMed  Google Scholar 

  6. Kaliberova LN, Krendelchtchikova V, Harmon DK, et al. CRAdRGDflt-IL-24 virotherapy in combination with chemotherapy of experimental glioma. Cancer Gene Ther. 2009;16:794–805.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Zerbini LF, Tamura RE, Correa RG, et al. Combinatorial effect of non-steroidal anti-inflammatory drugs and NF-kappaB inhibitors in ovarian cancer therapy. PLoS One. 2011;6:e24285.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Patani N, Douglas-Jones A, Mansel R, et al. Tumour suppressor function of MDA-7/IL-24 in human breast cancer. Cancer Cell Int. 2010;10:29.

    PubMed Central  PubMed  Google Scholar 

  9. Zhu Y, Lv H, Xie Y, et al. Enhanced tumor suppression by an ING4/IL-24 bicistronic adenovirus-mediated gene cotransfer in human non-small cell lung cancer cells. Cancer Gene Ther. 2011;18:627–36.

    Article  CAS  PubMed  Google Scholar 

  10. Yan S, Zhang H, Xie Y, et al. Recombinant human interleukin-24 suppresses gastric carcinoma cell growth in vitro and in vivo. Cancer Investig. 2010;28:85–93.

    Article  CAS  Google Scholar 

  11. Lebedeva IV, Su ZZ, Sarkar D, et al. Melanoma differentiation associated gene-7, mda-7/interleukin-24, induces apoptosis in prostate cancer cells by promoting mitochondrial dysfunction and inducing reactive oxygen species. Cancer Res. 2003;63:8138–44.

    CAS  PubMed  Google Scholar 

  12. Los M, Panigrahi S, Rashedi I, et al. Apoptin, a tumor-selective killer. Biochim Biophys Acta. 2009;1793:1335–42.

    Article  CAS  PubMed  Google Scholar 

  13. Yuan L, Zhang L, Dong X, Zhao H, Li S, Han D, et al. Apoptin selectively induces the apoptosis of tumor cells by suppressing the transcription of HSP70. Tumour Biol. 2013;34:577–85.

    Article  CAS  PubMed  Google Scholar 

  14. Lin B, Kolluri SK, Lin F, et al. Conversion of Bcl-2 from protector to killer by interaction with nuclear orphan receptor Nur77/TR3. Cell. 2004;116:527–40.

    Article  CAS  PubMed  Google Scholar 

  15. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100:57–70.

    Article  CAS  PubMed  Google Scholar 

  16. Jiang G, Jiang AJ, Cheng Q, et al. A dual-regulated oncolytic adenovirus expressing interleukin-24 sensitizes melanoma cells to temozolomide via the induction of apoptosis. Tumour Biol. 2013;34:1263–71.

    Article  CAS  PubMed  Google Scholar 

  17. Yacoub A, Park MA, Gupta P, et al. Caspase-, cathepsin-, and PERK-dependent regulation of MDA-7/IL-24-induced cell killing in primary human glioma cells. Mol Cancer Ther. 2008;7:297–313.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This study was supported by the funds from the Natural Science Foundation of Heilongjiang (QC2011C071), Dr. Wu Liande Fund (WLD-QN1110), and Heilongjiang Science and Technology Project Fund.

Conflicts of interest

None

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Lijie Yuan or Xinghan Liu.

Additional information

Lijie Yuan and Hengyu Zhao contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Yuan, L., Zhao, H., Zhang, L. et al. The efficacy of combination therapy using adeno-associated virus-mediated co-expression of apoptin and interleukin-24 on hepatocellular carcinoma. Tumor Biol. 34, 3027–3034 (2013). https://doi.org/10.1007/s13277-013-0867-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-013-0867-z

Keywords

Navigation