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Article

Enhanced therapeutic efficacy of adenovirus-mediated interleukin-24 gene therapy combined with ionizing radiotherapy for nasopharyngeal carcinoma

  • Authors:
    • Jisheng Liu
    • Yujuan Zhang
    • Peng Sun
    • Yufeng Xie
    • Jim Xiang
    • Jicheng Yang
  • View Affiliations / Copyright

    Affiliations: Department of ENT, The First Affiliated Hospital of Soochow University, Suzhou, P.R. China, Institute for Fetal Origin Diseases and Reproductive Medicine Center, The First Affiliated Hospital and Experiment Center of Soochow University, Suzhou, P.R. China, Cell and Molecular Biology Institute, College of Medicine, Soochow University, Suzhou, P.R. China, Department of Oncology and Immunology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada
  • Pages: 1165-1174
    |
    Published online on: June 19, 2013
       https://doi.org/10.3892/or.2013.2550
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Abstract

Melanoma differentiation-associated gene-7 (mda-7)/interleukin-24 (IL-24), a unique cytokine tumor suppressor, displays ubiquitous antitumor activities and cancer-specific cytotoxicities via multiple signaling pathways. In the present study, we investigated the antitumor effect of adenovirus-mediated IL-24 (AdVIL-24) gene therapy in conjunction with ionizing radiation on CNE-2Z human nasopharyngeal carcinoma (NPC) cells in vitro and in vivo in athymic nude mice, and its potential mechanisms. We demonstrated that AdVIL-24 gene therapy plus ionizing radiotherapy induced enhanced growth inhibition, cell cycle G1 phase arrest and apoptosis in vitro in CNE-2Z human NPC cells and in vivo in CNE-2Z xenografted tumors subcutaneously implanted in athymic nude mice. Mechanistically, AdVIL-24 combined with ionizing radiation led to the substantial upregulation of P21 and P27 cyclin-dependent kinase (CDK) inhibitors, ratio of pro-apoptotic to anti-apoptotic molecules Bax/Bcl-2 and cleaved caspase‑3 as well as downregulation of cyclin E and CDK2 in vitro and in vivo in CNE-2Z human NPC cells. Furthermore, AdVIL-24 plus radiation additively reduced the tumor vessel CD34 expression and microvessel density in vivo. More importantly, AdVIL-24 potentially blocked the radiation-induced enhancement of vascular endothelial growth factor (VEGF), a pro-angiogenic factor. The enhanced antitumor activity against NPC elicited by AdVIL-24 gene therapy combined with ionizing radiotherapy was closely associated with the enhanced induction of G1 phase arrest and apoptosis via additive modulation of cell cycle regulatory molecules and activation of intrinsic apoptotic pathways, and the overlapping inhibition of tumor angiogenesis. Thus, our results suggest that AdVIL-24 gene therapy combined with ionizing radiotherapy may be a novel and effective treatment strategy for human NPC.
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View References

1 

Wei WI and Sham JS: Nasopharyngeal carcinoma. Lancet. 365:2041–2054. 2005. View Article : Google Scholar : PubMed/NCBI

2 

Young LS and Rickinson AB: Epstein-Barr virus: 40 years on. Nat Rev Cancer. 4:757–768. 2004.PubMed/NCBI

3 

Spano JP, Busson P, Atlan D, Bourhis J, Pignon JP, Esteban C and Armand JP: Nasopharyngeal carcinomas: an update. Eur J Cancer. 39:2121–2135. 2003. View Article : Google Scholar : PubMed/NCBI

4 

Yu MC and Yuan JM: Epidemiology of nasopharyngeal carcinoma. Semin Cancer Biol. 12:421–429. 2002. View Article : Google Scholar : PubMed/NCBI

5 

Guigay J: Advances in nasopharyngeal carcinoma. Curr Opin Oncol. 20:264–269. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Lee AW, Yau TK, Wong DH, et al: Treatment of stage IV(A–B) nasopharyngeal carcinoma by induction-concurrent chemoradiotherapy and accelerated fractionation. Int J Radiat Oncol Biol Phys. 63:1331–1338. 2005.

7 

Le QT, Tate D, Koong A, et al: Improved local control with stereotactic radiosurgical boost in patients with nasopharyngeal carcinoma. Int J Radiat Oncol Biol Phys. 56:1046–1054. 2003. View Article : Google Scholar : PubMed/NCBI

8 

Lee AW, Sze WM, Au JS, et al: Treatment results for nasopharyngeal carcinoma in the modern era: the Hong Kong experience. Int J Radiat Oncol Biol Phys. 61:1107–1116. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Sauane M, Gopalkrishnan RV, Sarkar D, et al: MDA-7/IL-24: novel cancer growth suppressing and apoptosis inducing cytokine. Cytokine Growth Factor Rev. 14:35–51. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Fisher PB: Is mda-7/IL-24 a ‘magic bullet’ for cancer? Cancer Res. 65:10128–10138. 2005.

11 

Ramesh R, Mhashilkar AM, Tanaka F, et al: Melanoma differentiation-associated gene 7/interleukin (IL)-24 is a novel ligand that regulates angiogenesis via the IL-22 receptor. Cancer Res. 63:5105–5113. 2003.PubMed/NCBI

12 

Nishikawa T, Ramesh R, Munshi A, Chada S and Meyn RE: Adenovirus-mediated mda-7 (IL24) gene therapy suppresses angiogenesis and sensitizes NSCLC xenograft tumors to radiation. Mol Ther. 9:818–828. 2004. View Article : Google Scholar : PubMed/NCBI

13 

Caudell EG, Mumm JB, Poindexter N, et al: The protein product of the tumor suppressor gene, melanoma differentiation-associated gene 7, exhibits immunostimulatory activity and is designated IL-24. J Immunol. 168:6041–6046. 2002. View Article : Google Scholar

14 

Ramesh R, Ito I, Gopalan B, Saito Y, Mhashilkar AM and Chada S: Ectopic production of MDA-7/IL-24 inhibits invasion and migration of human lung cancer cells. Mol Ther. 9:510–518. 2004. View Article : Google Scholar : PubMed/NCBI

15 

Park MA, Yacoub A, Sarkar D, et al: PERK-dependent regulation of MDA-7/IL-24-induced autophagy in primary human glioma cells. Autophagy. 4:513–515. 2008. View Article : Google Scholar : PubMed/NCBI

16 

Yacoub A, Hamed HA, Allegood J, et al: PERK-dependent regulation of ceramide synthase 6 and thioredoxin play a key role in mda-7/IL-24-induced killing of primary human glioblastoma multiforme cells. Cancer Res. 70:1120–1129. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Hughes J, Alusi G and Wang Y: Gene therapy and nasopharyngeal carcinoma. Rhinology. 50:115–121. 2012.

18 

Li JH, Huang D, Sun BF, Zhang X, Middeldorp J, Klamut H and Liu FF: Efficacy of ionizing radiation combined with adenoviral p53 therapy in EBV-positive nasopharyngeal carcinoma. Int J Cancer. 87:606–610. 2000. View Article : Google Scholar : PubMed/NCBI

19 

Xie Y, Sheng W, Miao J, Xiang J and Yang J: Enhanced antitumor activity by combining an adenovirus harboring ING4 with cisplatin for hepatocarcinoma cells. Cancer Gene Ther. 18:176–188. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Su ZZ, Lebedeva IV, Sarkar D, et al: Ionizing radiation enhances therapeutic activity of mda-7/IL-24: overcoming radiation- and mda-7/IL-24-resistance in prostate cancer cells overexpressing the antiapoptotic proteins bcl-xL or bcl-2. Oncogene. 25:2339–2348. 2006. View Article : Google Scholar

21 

Emdad L, Sarkar D, Lebedeva IV, et al: Ionizing radiation enhances adenoviral vector expressing mda-7/IL-24-mediated apoptosis in human ovarian cancer. J Cell Physiol. 208:298–306. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Liu J, Sheng W, Xie Y, Shan Y, Miao J, Xiang J and Yang J: The in vitro and in vivo antitumor activity of adenovirus-mediated interleukin-24 expression for laryngocarcinoma. Cancer Biother Radiopharm. 25:29–38. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Wang X, Ye Z, Zhong J, Xiang J and Yang J: Adenovirus-mediated Il-24 expression suppresses hepatocellular carcinoma growth via induction of cell apoptosis and cycling arrest and reduction of angiogenesis. Cancer Biother Radiopharm. 22:56–63. 2007. View Article : Google Scholar : PubMed/NCBI

24 

Xie Y, Lv H, Sheng W, Miao J, Xiang J and Yang J: Synergistic tumor suppression by adenovirus-mediated inhibitor of growth 4 and interleukin-24 gene cotransfer in hepatocarcinoma cells. Cancer Biother Radiopharm. 26:681–695. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 25:402–408. 2001.

26 

Schmittgen TD and Livak KJ: Analyzing real-time PCR data by the comparative C(T) method. Nat Protoc. 3:1101–1108. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Madhusoodhanan R, Natarajan M, Veeraraghavan J, Herman TS and Aravindan N: NFkappaB activity and transcriptional responses in human breast adenocarcinoma cells after single and fractionated irradiation. Cancer Biol Ther. 8:765–773. 2009. View Article : Google Scholar

28 

Weidner N: Current pathologic methods for measuring intratumoral microvessel density within breast carcinoma and other solid tumors. Breast Cancer Res Treat. 36:169–180. 1995. View Article : Google Scholar

29 

Wang W, Qin SK, Chen BA and Chen HY: Experimental study on antitumor effect of arsenic trioxide in combination with cisplatin or doxorubicin on hepatocellular carcinoma. World J Gastroenterol. 7:702–705. 2001.PubMed/NCBI

30 

Li JH, Li P, Klamut H and Liu FF: Cytotoxic effects of Ad5CMV-p53 expression in two human nasopharyngeal carcinoma cell lines. Clin Cancer Res. 3:507–514. 1997.PubMed/NCBI

31 

Pan JJ, Zhang SW, Chen CB, et al: Effect of recombinant adenovirus-p53 combined with radiotherapy on long-term prognosis of advanced nasopharyngeal carcinoma. J Clin Oncol. 27:799–804. 2009. View Article : Google Scholar : PubMed/NCBI

32 

Weinrib L, Li JH, Donovan J, Huang D and Liu FF: Cisplatin chemotherapy plus adenoviral p53 gene therapy in EBV-positive and -negative nasopharyngeal carcinoma. Cancer Gene Ther. 8:352–360. 2001. View Article : Google Scholar : PubMed/NCBI

33 

Harper JW, Adami GR, Wei N, Keyomarsi K and Elledge SJ: The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclin-dependent kinases. Cell. 75:805–816. 1993. View Article : Google Scholar : PubMed/NCBI

34 

Toyoshima H and Hunter T: p27, a novel inhibitor of G1 cyclin-Cdk protein kinase activity, is related to p21. Cell. 78:67–74. 1994. View Article : Google Scholar : PubMed/NCBI

35 

Danial NN and Korsmeyer SJ: Cell death: critical control points. Cell. 116:205–219. 2004. View Article : Google Scholar : PubMed/NCBI

36 

Dvorak HF: Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol. 20:4368–4380. 2002. View Article : Google Scholar : PubMed/NCBI

37 

Moeller BJ, Cao Y, Li CY and Dewhirst MW: Radiation activates HIF-1 to regulate vascular radiosensitivity in tumors: role of reoxygenation, free radicals, and stress granules. Cancer Cell. 5:429–441. 2004. View Article : Google Scholar : PubMed/NCBI

38 

Camphausen K, Moses MA, Beecken WD, Khan MK, Folkman J and O’Reilly MS: Radiation therapy to a primary tumor accelerates metastatic growth in mice. Cancer Res. 61:2207–2211. 2001.PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Liu J, Zhang Y, Sun P, Xie Y, Xiang J and Yang J: Enhanced therapeutic efficacy of adenovirus-mediated interleukin-24 gene therapy combined with ionizing radiotherapy for nasopharyngeal carcinoma. Oncol Rep 30: 1165-1174, 2013.
APA
Liu, J., Zhang, Y., Sun, P., Xie, Y., Xiang, J., & Yang, J. (2013). Enhanced therapeutic efficacy of adenovirus-mediated interleukin-24 gene therapy combined with ionizing radiotherapy for nasopharyngeal carcinoma. Oncology Reports, 30, 1165-1174. https://doi.org/10.3892/or.2013.2550
MLA
Liu, J., Zhang, Y., Sun, P., Xie, Y., Xiang, J., Yang, J."Enhanced therapeutic efficacy of adenovirus-mediated interleukin-24 gene therapy combined with ionizing radiotherapy for nasopharyngeal carcinoma". Oncology Reports 30.3 (2013): 1165-1174.
Chicago
Liu, J., Zhang, Y., Sun, P., Xie, Y., Xiang, J., Yang, J."Enhanced therapeutic efficacy of adenovirus-mediated interleukin-24 gene therapy combined with ionizing radiotherapy for nasopharyngeal carcinoma". Oncology Reports 30, no. 3 (2013): 1165-1174. https://doi.org/10.3892/or.2013.2550
Copy and paste a formatted citation
x
Spandidos Publications style
Liu J, Zhang Y, Sun P, Xie Y, Xiang J and Yang J: Enhanced therapeutic efficacy of adenovirus-mediated interleukin-24 gene therapy combined with ionizing radiotherapy for nasopharyngeal carcinoma. Oncol Rep 30: 1165-1174, 2013.
APA
Liu, J., Zhang, Y., Sun, P., Xie, Y., Xiang, J., & Yang, J. (2013). Enhanced therapeutic efficacy of adenovirus-mediated interleukin-24 gene therapy combined with ionizing radiotherapy for nasopharyngeal carcinoma. Oncology Reports, 30, 1165-1174. https://doi.org/10.3892/or.2013.2550
MLA
Liu, J., Zhang, Y., Sun, P., Xie, Y., Xiang, J., Yang, J."Enhanced therapeutic efficacy of adenovirus-mediated interleukin-24 gene therapy combined with ionizing radiotherapy for nasopharyngeal carcinoma". Oncology Reports 30.3 (2013): 1165-1174.
Chicago
Liu, J., Zhang, Y., Sun, P., Xie, Y., Xiang, J., Yang, J."Enhanced therapeutic efficacy of adenovirus-mediated interleukin-24 gene therapy combined with ionizing radiotherapy for nasopharyngeal carcinoma". Oncology Reports 30, no. 3 (2013): 1165-1174. https://doi.org/10.3892/or.2013.2550
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