Novel oncolytic adenovirus sensitizes renal cell carcinoma cells to radiotherapy via mitochondrial apoptotic cell death

Chen,Ren-Fu; Li,Yue-Yan; Li,Lian-Tao; Cheng,Qian; Jiang,Guan; Zheng,Jun-Nian

doi:10.3892/mmr.2014.2987

March-2015 Volume 11 Issue 3

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March-2015 Volume 11 Issue 3

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Article

Novel oncolytic adenovirus sensitizes renal cell carcinoma cells to radiotherapy via mitochondrial apoptotic cell death

Authors:
- Ren-Fu Chen
- Yue-Yan Li
- Lian-Tao Li
- Qian Cheng
- Guan Jiang
- Jun-Nian Zheng
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Affiliations: Department of Urology, Affiliated Hospital of Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China, Jiangsu Key Laboratory of Biological Cancer Therapy, Xuzhou Medical College, Xuzhou, Jiangsu 221002, P.R. China
Pages: 2141-2146
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Published online on: November 20, 2014

https://doi.org/10.3892/mmr.2014.2987
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Abstract

Renal cell carcinoma is the most frequent kidney malignancy and patients with metastatic disease have a poor prognosis. Suppressed apoptosis and marked invasiveness are distinctive features of renal cell carcinoma. In the present study, a dual‑regulated oncolytic adenovirus expressing the interluekin (IL)‑24 gene (Ki67‑ZD55‑IL‑24) was constructed utilizing the Ki67 promoter to replace the native viral promoter of the E1A gene. Whether the combination of Ki67‑ZD55‑IL‑24‑mediated gene virotherapy and radiotherapy produced increased cytotoxicity in renal cell carcinoma cells via mitochondrial apoptotic cell death was investigated. The data indicated that this novel strategy has the potential to be further developed into an effective approach to treat renal cell carcinoma. The results showed that the combination of Ki67‑ZD55‑IL‑24 and radiotherapy significantly enhanced anti‑tumour activity via increasing the induction of apoptosis in melanoma cells compared with the other agents.

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1	Garcia JA and Rini BI: Recent progress in the management of advanced renal cell carcinoma. CA Cancer J Clin. 57:112–125. 2007. View Article : Google Scholar : PubMed/NCBI
2	Park MA, Hamed HA, Mitchell C, et al: A serotype 5/3 adenovirus expressing MDA-7/IL-24 infects renal carcinoma cells and promotes toxicity of agents that increase ROS and ceramide levels. Mol Pharmacol. 79:360–380. 2011. View Article : Google Scholar
3	Sunela KL, Kataja MJ, Lehtinen ET, et al: Prognostic factors and long-term survival in renal cell cancer patients. Scand J Urol Nephrol. 43:454–460. 2009. View Article : Google Scholar : PubMed/NCBI
4	Jiang G, Zhang L, Xin Y, et al: Conditionally replicating adenoviruses carrying mda-7/IL-24 for cancer therapy. Acta Oncol. 51:285–292. 2012. View Article : Google Scholar
5	Emdad L, Lebedeva IV, Su ZZ, et al: Historical perspective and recent insights into our understanding of the molecular and biochemical basis of the antitumor properties of mda-7/IL-24. Cancer Biol Ther. 8:391–400. 2009. View Article : Google Scholar : PubMed/NCBI
6	Colozza M, Sidoni A and Piccart-Gebhart M: Value of Ki67 in breast cancer: the debate is still open. Lancet Oncol. 11:414–415. 2010. View Article : Google Scholar : PubMed/NCBI
7	Pei DS, Qian GW, Tian H, et al: Analysis of human Ki-67 gene promoter and identification of the Sp1 binding sites for Ki-67 transcription. Tumour Biol. 33:257–266. 2012. View Article : Google Scholar
8	Zhao L, Gu J, Dong A, et al: Potent antitumor activity of oncolytic adenovirus expressing mda-7/IL-24 for colorectal cancer. Hum Gene Ther. 16:845–858. 2005. View Article : Google Scholar : PubMed/NCBI
9	Liu J, Fang L, Cheng Q, et al: Effects of G250 promoter controlled conditionally replicative adenovirus expressing Ki67-siRNA on renal cancer cell. Cancer Sci. 103:1880–1888. 2012. View Article : Google Scholar : PubMed/NCBI
10	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. 34:1263–1271. 2013. View Article : Google Scholar : PubMed/NCBI
11	Wang MJ, Pei DS, Qian GW, et al: p53 regulates Ki-67 promoter activity through p53- and Sp1-dependent manner in HeLa cells. Tumour Biol. 32:905–912. 2011. View Article : Google Scholar : PubMed/NCBI
12	Geoerger B, Grill J, Opolon P, et al: Potentiation of radiation therapy by the oncolytic adenovirus dl1520 (ONYX-015) in human malignant glioma xenografts. Br J Cancer. 89:577–584. 2003. View Article : Google Scholar : PubMed/NCBI
13	Freytag SO, Barton KN, Brown SL, et al: Replication-competent adenovirus-mediated suicide gene therapy with radiation in a preclinical model of pancreatic cancer. Mol Ther. 15:1600–1606. 2007. View Article : Google Scholar : PubMed/NCBI
14	Nandi S, Ulasov IV, Tyler MA, et al: Low-dose radiation enhances survivin-mediated virotherapy against malignant glioma stem cells. Cancer Res. 68:5778–5784. 2008. View Article : Google Scholar : PubMed/NCBI
15	Kuroda S, Fujiwara T, Shirakawa Y, et al: Telomerase-dependent oncolytic adenovirus sensitizes human cancer cells to ionizing radiation via inhibition of DNA repair machinery. Cancer Res. 70:9339–9348. 2010. View Article : Google Scholar : PubMed/NCBI
16	Yu de B, Zhong SY, Yang M, et al: Potent antitumor activity of double-regulated oncolytic adenovirus-mediated ST13 for colorectal cancer. Cancer Sci. 100:678–683. 2009. View Article : Google Scholar : PubMed/NCBI
17	Bhutia SK, Das SK, Azab B, et al: Targeting breast cancer-initiating/stem cells with melanoma differentiation-associated gene-7/interleukin-24. Int J Cancer. 133:2726–2736. 2013.PubMed/NCBI
18	Eulitt PJ, Park MA, Hossein H, et al: Enhancing mda-7/IL-24 therapy in renal carcinoma cells by inhibiting multiple protective signaling pathways using sorafenib and by Ad.5/3 gene delivery. Cancer Biol Ther. 10:1290–1305. 2010. View Article : Google Scholar : PubMed/NCBI
19	Park MA, Walker T, Martin AP, et al: MDA-7/IL-24-induced cell killing in malignant renal carcinoma cells occurs by a ceramide/CD95/PERK-dependent mechanism. Mol Cancer Ther. 8:1280–1291. 2009. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Novel oncolytic adenovirus sensitizes renal cell carcinoma cells to radiotherapy via mitochondrial apoptotic cell death

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