Synergistic Suppression Effect on Tumor Growth of Hepatocellular Carcinoma by Combining Oncolytic Adenovirus Carrying XAF1 with Cisplatin

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 2014 Sep 22

PMID 25240826

Citations 29

Authors

BuYun Ma

Yanchun Wang

Xiumei Zhou

Panpan Huang

Rong Zhang

Tao Liu

Caixia Cui

Xinyuan Liu

Yigang Wang

Affiliations

Soon will be listed here.

Abstract

Purpose: The potent anticancer efficacy of oncolytic viruses has been verified in Clinic in recent years. Cisplatin (DDP) is one of most common chemotherapeutic drugs, but is accompanied by side effects and drug resistance. Our previous studies have shown the strategy of cancer -targeting gene-viro-therapy (CTGVT) mediated by the oncolytic virus ZD55 containing the XAF1 cDNA (ZD55-XAF1), which exhibited potent antitumor effects in various tumor cells and no apparent toxicities on normal cells. In the study, the CTGVT strategy is broadened by combining DDP with ZD55-XAF1 for growth inhibition of hepatocellular carcinoma (HCC) cells.

Methods: The transgenic expression was evaluated by both in vitro and in vivo experiments, and the enhanced inhibitory effect of ZD55-XAF1 combined with cisplatin was assessed in HCC cells. The cytotoxicity on normal liver cells was evaluated by MTT assay and apoptotic cell staining. Activation of caspase-9 and PARP for apoptosis was further detected by Western blot analysis. The in vivo antitumor efficacy of combination treatment with cisplatin and ZD55-XAF1 was estimated in an HCC xenograft mouse model.

Results: We found that the combination of ZD55-XAF1 and cisplatin showed enhanced inhibitory effects on the proliferation of HCC cells in vitro and tumor growth in mice. Furthermore, the combined treatment of ZD55-XAF1 and DDP decreases the chemotherapy dose needed to achieve the same inhibitory effect without overlapping toxicities on normal liver cells and induces tumor cell apoptosis via the activation of caspase-9/PARP pathway.

Conclusion: Thus, these data suggest that the chemo-gene-viro-therapeutic strategy by combining ZD55-XAF1 and DDP reveals a novel therapeutic strategy for hepatocellular carcinoma.

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References

Fillastre J . Cisplatin nephrotoxicity. Toxicol Lett. 1989; 46(1-3):163-75. DOI: 10.1016/0378-4274(89)90125-2. View

Pan Q, Liu B, Liu J, Cai R, Wang Y, Qian C . Synergistic induction of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying TRAIL. Mol Cell Biochem. 2007; 304(1-2):315-23. DOI: 10.1007/s11010-007-9514-6. View

Breitbach C, Burke J, Jonker D, Stephenson J, Haas A, Chow L . Intravenous delivery of a multi-mechanistic cancer-targeted oncolytic poxvirus in humans. Nature. 2011; 477(7362):99-102. DOI: 10.1038/nature10358. View

Nishiyama M, Yamamoto W, Park J, Okamoto R, Hanaoka H, Takano H . Low-dose cisplatin and 5-fluorouracil in combination can repress increased gene expression of cellular resistance determinants to themselves. Clin Cancer Res. 1999; 5(9):2620-8. View

Tamm I, Kornblau S, Segall H, Krajewski S, Welsh K, Kitada S . Expression and prognostic significance of IAP-family genes in human cancers and myeloid leukemias. Clin Cancer Res. 2000; 6(5):1796-803. View

Zhao L, Gu J, Dong A, Zhang Y, Zhong L, He L . Potent antitumor activity of oncolytic adenovirus expressing mda-7/IL-24 for colorectal cancer. Hum Gene Ther. 2005; 16(7):845-58. DOI: 10.1089/hum.2005.16.845. View

Nakagawa Y, Abe S, Kurata M, Hasegawa M, Yamamoto K, Inoue M . IAP family protein expression correlates with poor outcome of multiple myeloma patients in association with chemotherapy-induced overexpression of multidrug resistance genes. Am J Hematol. 2006; 81(11):824-31. DOI: 10.1002/ajh.20656. View

Kelland L . The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer. 2007; 7(8):573-84. DOI: 10.1038/nrc2167. View

He G, Lei W, Wang S, Xiao R, Guo K, Xia Y . Overexpression of tumor suppressor TSLC1 by a survivin-regulated oncolytic adenovirus significantly inhibits hepatocellular carcinoma growth. J Cancer Res Clin Oncol. 2012; 138(4):657-70. DOI: 10.1007/s00432-011-1138-2. View

10.

Liu X, Gu J . Targeting gene-virotherapy of cancer. Cell Res. 2006; 16(1):25-30. DOI: 10.1038/sj.cr.7310005. View

11.

Ganly I, Kirn D, Eckhardt G, Rodriguez G, Soutar D, Otto R . A phase I study of Onyx-015, an E1B attenuated adenovirus, administered intratumorally to patients with recurrent head and neck cancer. Clin Cancer Res. 2000; 6(3):798-806. View

12.

Heise C, Sampson-Johannes A, Williams A, McCormick F, Von Hoff D, Kirn D . ONYX-015, an E1B gene-attenuated adenovirus, causes tumor-specific cytolysis and antitumoral efficacy that can be augmented by standard chemotherapeutic agents. Nat Med. 1997; 3(6):639-45. DOI: 10.1038/nm0697-639. View

13.

Fong W, Liston P, Rajcan-Separovic E, St Jean M, Craig C, Korneluk R . Expression and genetic analysis of XIAP-associated factor 1 (XAF1) in cancer cell lines. Genomics. 2000; 70(1):113-22. DOI: 10.1006/geno.2000.6364. View

14.

Dan H, Sun M, Kaneko S, Feldman R, Nicosia S, Wang H . Akt phosphorylation and stabilization of X-linked inhibitor of apoptosis protein (XIAP). J Biol Chem. 2003; 279(7):5405-12. DOI: 10.1074/jbc.M312044200. View

15.

Deveraux Q, Reed J . IAP family proteins--suppressors of apoptosis. Genes Dev. 1999; 13(3):239-52. DOI: 10.1101/gad.13.3.239. View

16.

Wu Y, Zhang K, Yue X, Wang Y, Yang Y, Li G . Enhancement of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying MDA-7/IL-24. Acta Pharmacol Sin. 2009; 30(4):467-77. PMC: 4002269. DOI: 10.1038/aps.2009.16. View

17.

Khuri F, Nemunaitis J, Ganly I, Arseneau J, Tannock I, Romel L . a controlled trial of intratumoral ONYX-015, a selectively-replicating adenovirus, in combination with cisplatin and 5-fluorouracil in patients with recurrent head and neck cancer. Nat Med. 2000; 6(8):879-85. DOI: 10.1038/78638. View

18.

Liston P, Fong W, Kelly N, Toji S, Miyazaki T, Conte D . Identification of XAF1 as an antagonist of XIAP anti-Caspase activity. Nat Cell Biol. 2001; 3(2):128-33. DOI: 10.1038/35055027. View

19.

Zou W, Luo C, Zhang Z, Liu J, Gu J, Pei Z . A novel oncolytic adenovirus targeting to telomerase activity in tumor cells with potent. Oncogene. 2004; 23(2):457-64. DOI: 10.1038/sj.onc.1207033. View

20.

Bisht S, Bhakta G, Mitra S, Maitra A . pDNA loaded calcium phosphate nanoparticles: highly efficient non-viral vector for gene delivery. Int J Pharm. 2004; 288(1):157-68. DOI: 10.1016/j.ijpharm.2004.07.035. View