A conditionally replicating adenovirus expressing IL-24 acts synergistically with temozolomide to enhance apoptosis in melanoma cells in vitro

Liang,Zhen; Yang,Chun‑Sheng; Gu,Feng; Zhang,Lan‑Sheng

doi:10.3892/ol.2017.6007

A conditionally replicating adenovirus expressing IL-24 acts synergistically with temozolomide to enhance apoptosis in melanoma cells in vitro

Authors:
- Zhen Liang
- Chun‑Sheng Yang
- Feng Gu
- Lan‑Sheng Zhang
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Affiliations: Department of Obstetrics and Gynecology, Xuzhou Central Hospital, Xuzhou, Jiangsu 221009, P.R. China, Department of Dermatology, Affiliated Huai'an Hospital of Xuzhou Medical University, Huaian, Jiangsu 223002, P.R. China, Clinical Laboratory, Xuzhou Tumor Hospital, Xuzhou, Jiangsu 221002, P.R. China, Department of Oncology, The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu 221002, P.R. China
Published online on: April 7, 2017 https://doi.org/10.3892/ol.2017.6007
Pages: 4185-4189
Copyright: © Liang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Malignant melanoma is characterized by suppressed apoptosis in tumor cells and high levels of invasion. Temozolomide (TMZ) is one of the most effective single chemotherapeutic agents for patients with malignant melanoma, but resistance develops quickly and frequently. Therapeutic cytokines such as interleukin‑24 (IL‑24) and conditionally replicating adenoviruses have exhibited promising results as complementary therapies. Thus, the present study hypothesized that a conditionally replicating adenovirus expressing IL‑24 combined with TMZ may exhibit increased antitumor activity compared with either treatment alone in melanoma A375 and M14 cell lines in vitro. The present study constructed an E1B‑55 gene‑deleted conditionally replicating adenovirus expressing the IL‑24 gene (ZD55‑IL‑24). IL‑24 was expressed at high levels in melanoma cells infected with ZD55‑IL‑24 in the presence of TMZ. The combination of ZD55‑IL‑24 + TMZ induced higher protein expression levels of the proapoptotic proteins B‑cell lymphoma‑2 (Bcl‑2)‑like protein 4 and phosphorylated protein, γ‑H2A histone family member X (γ‑H2AX), and reduced the levels of the antiapoptotic proteins Bcl‑2, myeloid cell leukemia‑1and nuclear factor‑κB compared with either treatment individually. A dose‑dependent increase in the cytopathic effects for the combination of ZD55‑IL‑24 and TMZ was also observed. The data of the present study suggest that the ZD55‑IL‑24 + TMZ combination induced increased levels of apoptosis, possibly by triggering DNA damage, in melanoma cells in vitro compared with either treatment alone. These findings suggest that this strategy may be a promising approach for the treatment of patients with malignant melanoma.

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1	La Porta CA: Mechanism of drug sensitivity and resistance in melanoma. Curr Cancer Drug Targets. 9:391–397. 2009. View Article : Google Scholar : PubMed/NCBI
2	Nath K, Nelson DS, Ho AM, Lee SC, Darpolor MM, Pickup S, Zhou R, Heitjan DF, Leeper DB and Glickson JD: (31) P and (1) H MRS of DB-1 melanoma xenografts: Lonidamine selectively decreases tumor intracellular pH and energy status and sensitizes tumors to melphalan. NMR Biomed. 26:98–105. 2013. View Article : Google Scholar : PubMed/NCBI
3	Jiang G, Li RH, Sun C, Jia HY, Lei TC and Liu YQ: Efficacy and safety between temozolomide alone and temozolomide-based double therapy for malignant melanoma: A meta-analysis. Tumour Biol. 35:315–322. 2014. View Article : Google Scholar : PubMed/NCBI
4	Plummer ER, Middleton MR, Jones C, Olsen A, Hickson I, McHugh P, Margison GP, McGown G, Thorncroft M, Watson AJ, et al: Temozolomide pharmacodynamics in patients with metastatic melanoma: DNA damage and activity of repair enzymes O6-alkylguanine alkyltransferase and poly(ADP-ribose) polymerase-1. Clin Cancer Res. 11:3402–3409. 2005. View Article : Google Scholar : PubMed/NCBI
5	Jiang G, Li LT, Xin Y, Zhang L, Liu YQ and Zheng JN: Strategy for reversing resistance to temozolomide in malignant melanoma. Curr Med Chem. 19:3886–3892. 2012. View Article : Google Scholar : PubMed/NCBI
6	Jiang G, Liu YQ, Wei ZP, Pei DS, Mao LJ and Zheng JN: Enhanced anti-tumor activity by the combination of a conditionally replicating adenovirus mediated interleukin-24 and dacarbazine against melanoma cells via induction of apoptosis. Cancer Lett. 294:220–228. 2010. View Article : Google Scholar : PubMed/NCBI
7	Tian H, Zhang DF, Zhang BF, Li HZ, Zhang Q, Li LT, Pei DS and Zheng JN: Melanoma differentiation associated gene-7/interleukin-24 induces caspase-3 denitrosylation to facilitate the activation of cancer cell apoptosis. J Interferon Cytokine Res. 35:157–167. 2015. View Article : Google Scholar : PubMed/NCBI
8	Dent P, Yacoub A, Hamed HA, Park MA, Dash R, Bhutia SK, Sarkar D, Wang XY, Gupta P, Emdad L, et al: The development of MDA-7/IL-24 as a cancer therapeutic. Pharmacol Ther. 128:375–384. 2010. View Article : Google Scholar : PubMed/NCBI
9	Emdad L, Lebedeva IV, Su ZZ, Gupta P, Sauane M, Dash R, Grant S, Dent P, Curiel DT, Sarkar D and Fisher PB: 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
10	Zheng M, Bocangel D, Ramesh R, Ekmekcioglu S, Poindexter N, Grimm EA and Chada S: Interleukin-24 overcomes temozolomide resistance and enhances cell death by down-regulation of O6-methylguanine-DNA methyltransferase in human melanoma cells. Mol Cancer Ther. 7:3842–3851. 2008. View Article : Google Scholar : PubMed/NCBI
11	Liu XY: Targeting gene-virotherapy of cancer and its prosperity. Cell Res. 16:879–886. 2006. View Article : Google Scholar : PubMed/NCBI
12	Liu XY, Li HG, Zhang KJ and Gu JF: Strategy of Cancer Targeting Gene-Viro-Therapy (CTGVT) a trend in both cancer gene therapy and cancer virotherapy. Curr Pharm Biotechnol. 13:1761–1767. 2012. View Article : Google Scholar : PubMed/NCBI
13	Zhao L, Gu J, Dong A, Zhang Y, Zhong L, He L, Wang Y, Zhang J, Zhang Z, Huiwang J, 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
14	Zhang ZY, Wang LQ, Fu CF, Li X, Cui ZL, Zhang JY, Xue SH, Sun N and Xu F: Combination of targeting gene-viro therapy with recombinant Fowl-pox viruses with HN and VP3 genes on mouse osteosarcoma. Eur Rev Med Pharmacol Sci. 17:767–776. 2013.PubMed/NCBI
15	Jiang G, Jiang AJ, Cheng Q, Tian H, Li LT and Zheng JN: 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
16	Zhou X, Xie G, Wang S, Wang Y, Zhang K, Zheng S, Chu L, Xiao L, Yu Y, Zhang Y and Liu X: Potent and specific antitumor effect for colorectal cancer by CEA and Rb double regulated oncolytic adenovirus harboring ST13 gene. PLos One. 7:e475662012. View Article : Google Scholar : PubMed/NCBI
17	Jiang G, Zhang L, Xin Y, Pei DS, Wei ZP, Liu YQ and Zheng JN: Conditionally replicating adenoviruses carrying mda-7/IL-24 for cancer therapy. Acta Oncol. 51:285–292. 2012. View Article : Google Scholar : PubMed/NCBI
18	Zhao L, Dong A, Gu J, Liu Z, Zhang Y, Zhang W, Wang Y, He L, Qian C, Qian Q and Liu X: The antitumor activity of TRAIL and IL-24 with replicating oncolytic adenovirus in colorectal cancer. Cancer Gene Ther. 13:1011–1022. 2006. View Article : Google Scholar : PubMed/NCBI
19	Qiu S, Ruan H, Pei Z, Hu B, Lan P, Wang J, Zhang Z, Gu J, Sun L, Qian C, et al: Combination of targeting gene-virotherapy with 5-FU enhances antitumor efficacy in malignant colorectal carcinoma. J Interferon Cytokine Res. 24:219–230. 2004. View Article : Google Scholar : PubMed/NCBI
20	Berger A, Quast SA, Plötz M, Hein M, Kunz M, Langer P and Eberle J: Sensitization of melanoma cells for death ligand-induced apoptosis by an indirubin derivative-Enhancement of both extrinsic and intrinsic apoptosis pathways. Biochem Pharmacol. 81:71–81. 2011. View Article : Google Scholar : PubMed/NCBI
21	Kong XJ, Duan LJ, Qian XQ, Xu D, Liu HL, Zhu YJ and Qi J: Tumor-suppressive microRNA-497 targets IKKβ to regulate NF-κB signaling pathway in human prostate cancer cells. Am J Cancer Res. 5:1795–1804. 2015.PubMed/NCBI
22	Wilczynski J, Duechler M and Czyz M: Targeting NF-κB and HIF-1 pathways for the treatment of cancer: Part I. Arch Immunol Ther Exp (Warsz). 59:289–299. 2011. View Article : Google Scholar : PubMed/NCBI