Synergistic antitumor effect of the combination of a dual cancer‑specific oncolytic adenovirus and cisplatin on lung cancer cells

Jin,Jing; Zhu,Yilong; Sun,Fei; Chen,Zhifei; Chen,Shuang; Li,Yiquan; Li,Wenjie; Li,Min; Cui,Chuanxin; Cui,Yingli; Yin,Xunzhi; Li,Shanzhi; Zhao,Jin; Yan,Guo; Li,Xiao; Jin,Ningyi

doi:10.3892/ol.2018.9470

Synergistic antitumor effect of the combination of a dual cancer‑specific oncolytic adenovirus and cisplatin on lung cancer cells

Authors:
- Jing Jin
- Yilong Zhu
- Fei Sun
- Zhifei Chen
- Shuang Chen
- Yiquan Li
- Wenjie Li
- Min Li
- Chuanxin Cui
- Yingli Cui
- Xunzhi Yin
- Shanzhi Li
- Jin Zhao
- Guo Yan
- Xiao Li
- Ningyi Jin
View Affiliations

Affiliations: Institute of Frontier Medical Science, Jilin University, Changchun, Jilin 130021, P.R. China, Academicians Workstation of Jilin Province, Changchun University of Chinese Medicine, Changchun, Jilin 130117, P.R. China, Key Laboratory of Jilin Province for Zoonosis Prevention and Control, Institute of Military Veterinary Medicine, Academy of Military Medical Sciences, Changchun, Jilin 130122, P.R. China
Published online on: September 20, 2018 https://doi.org/10.3892/ol.2018.9470
Pages: 6275-6282
Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

The effect of the combination of a recombinant adenovirus (ATV) expressing a specific apoptin protein and cisplatin on human lung cancer cells (A549 cells) was determined. The inhibitory effects of ATV and cisplatin, ATV alone, or cisplatin alone on the migration and invasion of A549 cells were evaluated in vitro using cell proliferation, wound healing, Transwell migration and Matrigel invasion assays. The tumor inhibition effect on A549 cells in vivo was assessed by observing the tumor growth and survival rate of nude mice with subcutaneous tumor xenografts grown from implanted A549 cells after treatment with ATV, cisplatin, or ATV combined with cisplatin. The proliferation (P<0.01), migration (P<0.01), and invasion (P<0.01) on A549 cells was suppressed significantly by ATV, cisplatin, and ATV and cisplatin, in a dose‑ and time‑dependent manner. The inhibition of tumor growth in transplanted nude mice in the ATV combined with cisplatin group was significantly higher than that displayed in the other groups, and the survival rate of the combined treatment group was significantly higher than that of the group treated with cisplatin alone. The results indicated that the combined application of ATV and cisplatin could reduce toxicity and showed a synergistic effect in reducing tumor growth and increasing survival. Thus, there is a potential research value in treating tumors using the combination of ATV and cisplatin, which provides a foundation for future preclinical studies on this antitumor treatment.

View Figures

View References

1	Chen W, Zheng R, Zhang S, Zeng H, Zou X and He J: Report of Cancer Incidence and Mortality in China, 2013. China Cancer. 25:1–8. 2017.(In Chinese). View Article : Google Scholar
2	Min YC: The development in the study of platinum-based antineoplastic drugs. Chin J Mod Drug Appl. 9:2822015.
3	Brabec V and Kasparkova J: Molecular aspects of resistance to antitumor platinum drugs. Drug Resist Updat. 5:147–161. 2002. View Article : Google Scholar : PubMed/NCBI
4	Arany I and Safirstein RL: Cisplatin nephrotoxicity. Semin Nephrol. 23:460–464. 2003. View Article : Google Scholar : PubMed/NCBI
5	Ali BH and Al Moundhri MS: Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: A review of some recent research. Food Chem Toxicol. 44:1173–1183. 2006. View Article : Google Scholar : PubMed/NCBI
6	Christova TY, Gorneva GA, Taxirov SI, Duridanova DB and Setchenska MS: Effect of cisplatin and cobalt chloride on antioxidant enzymes in the livers of Lewis lung carcinoma-bearing mice: Protective role of heme oxygenase. Toxicol Lett. 138:235–242. 2003. View Article : Google Scholar : PubMed/NCBI
7	Spracklen TF, Vorster AA, Ramma L, Dalvie S and Ramesar RS: Promoter region variation in NFE2L2 influences susceptibility to ototoxicity in patients exposed to high cumulative doses of cisplatin. Pharmacogenomics J. 17:515–520. 2017. View Article : Google Scholar : PubMed/NCBI
8	Maddika S, Mendoza FJ, Hauff K, Zamzow CR, Paranjothy T and Los M: Cancer-selective therapy of the future: Apoptin and its mechanism of action. Cancer Biol Ther. 5:10–19. 2006. View Article : Google Scholar : PubMed/NCBI
9	Leliveld SR, Dame RT, Mommaas MA, Koerten HK, Wyman C, Danen-van Oorschot AA, Rohn JL, Noteborn MH and Abrahams JP: Apoptin protein multimers form distinct higher-order nucleoprotein complexes with DNA. Nucleic Acids Res. 31:4805–4813. 2003. View Article : Google Scholar : PubMed/NCBI
10	Zhong X, Zhao H, Liang S, Zhou D, Zhang W and Yuan L: Gene delivery of apoptin-derived peptide using an adeno-associated virus vector inhibits glioma and prolongs animal survival. Biochem Biophys Res Commun. 482:506–513. 2017. View Article : Google Scholar : PubMed/NCBI
11	Zhang J, Hou L, Wu X, Zhao D, Wang Z, Hu H, Fu Y and He J: Inhibitory effect of genetically engineered mesenchymal stem cells with Apoptin on hepatoma cells in vitro and in vivo. Mol Cell Biochem. 416:193–203. 2016. View Article : Google Scholar : PubMed/NCBI
12	Gupta SK, Tiwari AK, Gandham RK and Sahoo AP: Combined administration of the apoptin gene and poly (I:C) induces potent anti-tumor immune response and inhibits growth of mouse mammary tumors. Int Immunopharmacol. 35:163–173. 2016. View Article : Google Scholar : PubMed/NCBI
13	Vragniau C, Hubner JM, Beidler P, Gil S, Saydaminova K, Lu ZZ, Yumul R, Wang H, Richter M, Sova P, et al: Studies on the interaction of tumor-derived HD5 alpha defensins with adenoviruses and implications for oncolytic adenovirus therapy. J Virol. 91:pii: e02030–16. 2017. View Article : Google Scholar
14	Mato-Berciano A, Raimondi G, Maliandi MV, Alemany R, Montoliu L and Fillat C: A NOTCH-sensitive uPAR-regulated oncolytic adenovirus effectively suppresses pancreatic tumor growth and triggers synergistic anticancer effects with gemcitabine and nab-paclitaxel. Oncotarget. 8:22700–22715. 2017. View Article : Google Scholar : PubMed/NCBI
15	Li X, Wang P, Li H, Du X, Liu M, Huang Q, Wang Y and Wang S: The efficacy of oncolytic adenovirus is mediated by T-cell responses against virus and tumor in syrian hamster model. Clin Cancer Res. 23:239–249. 2017. View Article : Google Scholar : PubMed/NCBI
16	Kim SY, Kang D, Choi HJ, Joo Y, Kim JH and Song JJ: Prime-boost immunization by both DNA vaccine and oncolytic adenovirus expressing GM-CSF and shRNA of TGF-β2 induces anti-tumor immune activation. Oncotarget. 8:15858–15877. 2017.PubMed/NCBI
17	Wang S, Shu J, Chen L, Chen X, Zhao J, Li S, Mou X and Tong X: Synergistic suppression effect on tumor growth of ovarian cancer by combining cisplatin with a manganese superoxide dismutase-armed oncolytic adenovirus. Onco Targets Ther. 9:6381–6388. 2016. View Article : Google Scholar : PubMed/NCBI
18	Ma B and Wang Y, Zhou X, Huang P, Zhang R, Liu T, Cui C, Liu X and Wang Y: Synergistic suppression effect on tumor growth of hepatocellular carcinoma by combining oncolytic adenovirus carrying XAF1 with cisplatin. J Cancer Res Clin Oncol. 141:419–429. 2015. View Article : Google Scholar : PubMed/NCBI
19	Qi Y, Guo H, Hu N, He D, Zhang S, Chu Y, Huang Y, Li X, Sun L and Jin N: Preclinical pharmacology and toxicology study of Ad-hTERT-E1a-Apoptin, a novel dual cancer-specific oncolytic adenovirus. Toxicol Appl Pharmacol. 280:362–369. 2014. View Article : Google Scholar : PubMed/NCBI
20	Zhang M, Wang J, Li C, Hu N, Wang K, Ji H, He D, Quan C, Li X, Jin N and Li Y: Potent growth-inhibitory effect of a dual cancer-specific oncolytic adenovirus expressing apoptin on prostate carcinoma. Int J Oncol. 42:1052–1060. 2013. View Article : Google Scholar : PubMed/NCBI
21	Liu L, Wu W, Zhu G, Liu L, Guan G, Li X, Jin N and Chi B: Therapeutic efficacy of an hTERT promoter-driven oncolytic adenovirus that expresses apoptin in gastric carcinoma. Int J Mol Med. 30:747–754. 2012. View Article : Google Scholar : PubMed/NCBI
22	Li X, Liu Y, Wen Z, Li C, Lu H, Tian M, Jin K, Sun L, Gao P, Yang E, et al: Potent anti-tumor effects of a dual specific oncolytic adenovirus expressing apoptin in vitro and in vivo. Mol Cancer. 9:102010. View Article : Google Scholar : PubMed/NCBI
23	Yin XZ, Chen S, Li WJ, Zhu YL, Li YQ, Cui CX, Li M, Cui YL, Zhao J, Li SZ, et al: Inhibitory effect of apopotin-loaded oncolytic adenovirus ATV on human cervical carcinoma HeLa cells. Chin J Cancer Biother. 24:1356–1361. 2017.(In Chinese).
24	Wang X, Xu L, Wu Q, Liu M, Tang F, Cai Y, Fan W, Huang H and Gu X: Inhibition of LDHA deliver potential anticancer performance in renal cell carcinoma. Urol Int. 99:237–244. 2017. View Article : Google Scholar : PubMed/NCBI
25	Robinson S and Galanis E: Potential and clinical translation of oncolytic measles viruses. Expert Opin Biol Ther. 17:353–363. 2017. View Article : Google Scholar : PubMed/NCBI
26	Ungerechts G, Bossow S, Leuchs B, Holm PS, Rommelaere J, Coffey M, Coffin R, Bell J and Nettelbeck DM: Moving oncolytic viruses into the clinic: Clinical-grade production, purification, and characterization of diverse oncolytic viruses. Mol Ther Methods Clin Dev. 3:160182016. View Article : Google Scholar : PubMed/NCBI
27	Patil S, Rao RS and Majumdar B: Clinical trials with oncolytic viruses: Current and future prospects. J Contemp Dent Pract. 16:i–ii. 2015.
28	Burke J, Nieva J, Borad MJ and Breitbach CJ: Oncolytic viruses: Perspectives on clinical development. Curr Opin Virol. 13:55–60. 2015. View Article : Google Scholar : PubMed/NCBI
29	Štefančíková L, Lacombe S, Salado D, Porcel E, Pagáčová E, Tillement O, Lux F, Depeš D, Kozubek S and Falk M: Effect of gadolinium-based nanoparticles on nuclear DNA damage and repair in glioblastoma tumor cells. J Nanobiotechnology. 14:632016. View Article : Google Scholar : PubMed/NCBI
30	Sengupta S, Mantha AK, Song H, Roychoudhury S, Nath S, Ray S and Bhakat KK: Elevated level of acetylation of APE1 in tumor cells modulates DNA damage repair. Oncotarget. 7:75197–75209. 2016. View Article : Google Scholar : PubMed/NCBI