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Journal of Cancer Research and Clinical Oncology

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01.12.2010 | Original Paper

The efficacy of combination therapy using adeno-associated virus-TRAIL targeting to telomerase activity and cisplatin in a mice model of hepatocellular carcinoma

verfasst von: Yigang Wang, Fang Huang, Haibo Cai, Yumei Wu, Guoqing He, Wen-Song Tan

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 12/2010

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Abstract

Purpose

TNF-related apoptosis-inducing ligand (TRAIL) functions as a soluble cytokine and has been demonstrated significant antitumor activity against a variety of cancer cell lines without toxicity to most normal cells. Cisplatin is a potent anticancer agent and is widely used in the clinical for treatment of human cancers. Adeno-associated virus (AAV2) is a promising gene delivery vehicle for its advantage of low pathogenicity and long-term gene expression. However, lack of tissue specificity caused low efficiency of AAV transfer to target cells. The promoter of human telomerase reverse transcriptase (hTERT) is a good candidate to enhance targeting efficiency of AAV in cancer cells. Although AAV-mediated TRAIL controlled by hTERT promoter (AAV-hTERT-TRAIL) has obvious antitumor activity, the tumor cannot be completely eradicated. In this study, we first examined the effectiveness of combination therapy of cisplatin and AAV-hTERT-TRAIL on human hepatocellular carcinoma (HCC) in vitro and in vivo.

Methods

For in vitro experiments, tumor cell lines were treated with cisplatin, virus, or both. The transgene TRAIL expression controlled by hTERT promoter was evaluated in BEL7404 HCC cell line. Cytotoxicity was performed by MTT analysis. Cell apoptosis was detected by flow cytometry analysis. The in vivo antitumor efficacy of combination treatment with cisplatin and AAV-hTERT-TRAIL was assessed in human hepatocellular carcinoma xenografts mouse model.

Results

The enhanced TRAIL expression was observed in BEL7404 cells treated with AAV-hTERT-TRAIL plus cisplatin. Treatment with both AAV-hTERT-TRAIL and cisplatin exhibited stronger cytotoxicity and induced more significant apoptosis in cancer cells compared with AAV-hTERT-TRAIL or cisplatin alone, respectively. Moreover, in animal experiments, the combined treatment greatly suppressed tumor growth and resulted in tumor cell death.

Conclusions

AAV-mediated therapeutic gene expression in combination with chemotherapy provides a promising therapeutic strategy for human cancers. These data suggest that combined use of AAV-hTERT-TRAIL and cisplatin may have potential clinical application.

Adam M, Bayer C, Henke J, Grosu A, Molls M, Nieder C (2008) Tirapazamine plus cisplatin and irradiation in a mouse model: improved tumor control at the cost of increased toxicity. J Cancer Res Clin Oncol 134:137–146CrossRefPubMed

Arany I, Safirstein RL (2003) Cisplatin Nephrotoxicity. Semin Nephrol 23:460–464CrossRefPubMed

Ashkenazi A, Pai RC, Fong S, Leung S, Lawrence DA, Marsters SA, Blackie C, Chang L, Mcmurtrey AE, Hebert A, Deforge L, Koumenis IL, Lewis D, Harris L, Bussiere J, Koeppen H, Shahrokh Z, Schwall RH (1999) Safety and antitumor activity of recombinant soluble Apo2 ligand. J Clin Invest 104:155–162CrossRefPubMed

Büning H, Perabo L, Coutelle O, Quadt-Humme S, Hallek M (2008) Recent developments in adeno-associated virus vector technology. J Gene Med 10:717–733CrossRefPubMed

Chinnaiyan AM, Prasad U, Shankar S, Hamstra DA, Shanaiah M, Chenevert TL, Ross BD, Rehemtulla A (2000) Combined effect of tumor necrosis factor-related apoptosis-inducing ligand and ionizing radiation in breast cancer therapy. Proc Natl Acad Sci USA 97:1754–1759CrossRefPubMed

Daniels RA, Turley H, Kimberley FC, Liu XS, Mongkolsapaya J, Ch’En P, Xu XN, Jin BQ, Pezzella F, Screaton GR (2005) Expression of TRAIL and TRAIL receptors in normal and malignant tissues. Cell Res 15:430–438CrossRefPubMed

Ichikawa K, Liu W, Zhao L, Wang Z, Liu D, Ohtsuka T, Zhang H, Mountz JD, Koopman WJ, Kimberly RP, Zhou T (2001) Tumoricidal activity of a novel antihuman DR5 monoclonal antibody without hepatocyte cytotoxicity. Nat Med 7:954–960CrossRefPubMed

Jin H, Yang R, Fong S, Totpal K, Lawrence D, Zheng Z, Ross J, Koeppen H, Schwall R, Ashkenazi A (2004) Apo2 ligand/tumor necrosis factor-related apoptosis-inducing ligand cooperates with chemotherapy to inhibit orthotopic lung tumor growth and improve survival. Cancer Res 64:4900–4905CrossRefPubMed

Jo M, Kim TH, Seol DW, Esplen JE, Dorko K, Billiar TR, Strom SC (2000) Apoptosis induced in normal human hepatocytes by tumor necrosis factor-related apoptosis-inducing ligand. Nat Med 6:564–567CrossRefPubMed

Keane MM, Ettenberg SA, Nau MM, Russell EK, Lipkowitz S (1999) Chemotherapy augments TRAIL-induced apoptosis in breast cell lines. Cancer Res 59:734–741PubMed

Kelland L (2007) The resurgence of platinum-based cancer chemotherapy. Nat Rev Cancer 7:573–584CrossRefPubMed

Kim K, Fisher MJ, Xu SQ, el-Deiry WS (2000) Molecular determinants of response to TRAIL in killing of normal and cancer cells. Clin Cancer Res 6:335–346PubMed

Kruyt FA (2008) TRAIL and cancer therapy. Cancer Lett 263:14–25CrossRefPubMed

LeBlanc HN, Ashkenazi A (2003) Apo2L/TRAIL and its death and decoy receptors. Cell Death Differ 10:66–75CrossRefPubMed

Lee SH, Shin MS, Kim HS, Lee HK, Park WS, Kim SY, Lee JH, Han SY, Park JY, Oh RR, Jang JJ, Han JY, Lee JY, Yoo NJ (1999) Alterations of the DR5/TRAIL receptor 2 gene in non-small cell lung cancers. Cancer Res 59:5683–5686PubMed

Lin T, Huang X, Gu J, Zhang L, Roth JA, Xiong M, Curley SA, Yu Y, Hunt KK, Fang B (2002) Long-term tumor-free survival from treatment with the GFPTRAIL fusion gene expressed from the hTERT promoter in breast cancer cells. Oncogene 21:8020–8028CrossRefPubMed

Liu J, Zou WG, Lang MF, Luo J, Sun LY, Wang XN, Qian QJ, Liu XY (2002) Cancer-specific killing by the CD suicide gene using the human telomerase reverse transcriptase promoter. Int J Oncol 21:661–666PubMed

Mingozzi F, Maus MV, Hui DJ, Sabatino DE, Murphy SL, Rasko JE, Ragni MV, Manno CS, Sommer J, Jiang H, Pierce GF, Ertl HC, High KA (2007) CD8(+) T-cell responses to adeno-associated virus capsid in humans. Nat Med 13:419–422CrossRefPubMed

Monahan PE, Jooss K, Sands MS (2002) Safety of adeno-associated virus gene therapy vectors: a current evaluation. Expert Opin Drug Saf 1:79–91CrossRefPubMed

Muzio M, Chinnaiyan AM, Kischkel FC, O’Rourke K, Shevchenko A, Ni J, Scaffidi C, Bretz JD, Zhang M, Gentz R, Mann M, Krammer PH, Peter ME, Dixit VM (1996) FLICE, a novel FADD-homologous ICE/CED-3-like protease, is recruited to the CD95 (Fas/APO-1) death-inducing signaling complex. Cell 85:817–827CrossRefPubMed

Nagane M, Pan G, Weddle JJ, Dixit VM, Cavenee WK, Huang HJ (2000) Increased death receptor 5 expression by chemotherapeutic agents in human gliomas causes synergistic cytotoxicity with tumor necrosis factor-related apoptosis inducing ligand in vitro and in vivo. Cancer Res 60:847–853PubMed

Pan QW, Liu BS, Liu J, Cai R, Wang YG, Qian C (2007a) Synergistic induction of tumor cell death by combining cisplatin with an oncolytic adenovirus carrying TRAIL. Mol Cell Biochem 304:315–323CrossRefPubMed

Pan QW, Zhong SY, Liu BS, Liu J, Cai R, Wang YG, Liu XY, Qian C (2007b) Enhanced sensitivity of hepatocellular carcinoma cells to chemotherapy with a Smac-armed oncolytic adenovirus. Acta Pharmacol Sin 28:1996–2004CrossRefPubMed

Pitti RM, Marsters SA, Ruppert S, Donahue CJ, Moore A, Ashkenazi A (1996) Induction of apoptosis by Apo-2 ligand, a new member of the tumor necrosis factor cytokine family. J Biol Chem 271:12687–12690CrossRefPubMed

Qiu S, Ruan H, Pei Z, Hu B, Lan P, Wang J, Zhang Z, Gu J, Sun L, Qian C, Liu X, Qi Y (2004) Combination of Targeting Gene-ViroTherapy with 5-FU enhances antitumor efficacy in malignant colorectal carcinoma. J Interferon Cytokine Res 24:219–230CrossRefPubMed

Schenk M, Weiss TS, Gregor M, Bitzer M (2003) Adenoviral gene transfer of tumor necrosis factor-related apoptosis-inducing ligand overcomes an impaired response of hepatoma cells but causes severe apoptosis in primary human hepatocytes. Cancer Res 63:2369–2372PubMed

Shi J, Zheng D, Liu Y, Sham MH, Tam P, Farzaneh F, Xu R (2005) Overexpression of soluble TRAIL induces apoptosis in human lung adenocarcinoma and inhibits growth of tumor xenografts in nude mice. Cancer Res 65:1687–1692CrossRefPubMed

Shin MS, Kim HS, Lee SH, Park WS, Kim SY, Park JY, Lee JH, Lee SK, Lee SN, Jung SS, Han JY, Kim H, Lee JY, Yoo NJ (2001) Mutations of tumor necrosis factor-related apoptosis-inducing ligand receptor 1 (TRAIL-R1) and receptor 2 (TRAIL-R2) genes in metastatic breast cancers. Cancer Res 61:4942–4946PubMed

Spierings DC, de Vries EG, Vellenga E, van den Heuvel FA, Koornstra JJ, Wesseling J, Hollema H, de Jong S (2004) Tissue distribution of the death ligand TRAIL and its receptors. J Histochem Cytochem 52:821–831CrossRefPubMed

Vandenberghe LH, Wilson JM (2007) AAV as an immunogen. Curr Gene Ther 7:325–333CrossRefPubMed

Verweij J, de Wit R, de Mulder PH (1996) Optimal control of acute cisplatin-induced emesis. Oncology 53(Suppl 1):56–64CrossRefPubMed

Voelkel-Johnson C, King DL, Norris JS (2002) Resistance of prostate cancer cells to soluble TNF-related apoptosis-inducing ligand (TRAIL/Apo2L) can be overcome by doxorubicin or adenoviral delivery of full-length TRAIL. Cancer Gene Ther 9:164–172CrossRefPubMed

Walczak H, Miller RE, Ariail K, Gliniak B, Griffith TS, Kubin M, Chin W, Jones J, Woodward A, Le T, Smith C, Smolak P, Goodwin RG, Rauch CT, Schuh JC, Lynch DH (1999) Tumoricidal activity of tumor necrosis factor-related apoptosis-inducing ligand in vivo. Nat Med 5:157–163CrossRefPubMed

Wang YG, Wang JH, Zhang YH, Gu Q, Liu XY (2004) Antitumor effect of a novel adeno-associated virus vector targeting to telomerase activity in tumor cells. Acta Biochim Biophys Sin 36:492–500CrossRefPubMed

Wang X, Su C, Cao H, Li K, Chen J, Jiang L, Zhang Q, Wu X, Jia X, Liu Y, Wang W, Liu X, Wu M, Qian Q (2008) A novel triple-regulated oncolytic adenovirus carrying p53 gene exerts potent antitumor efficacy on common human solid cancers. Mol Cancer Ther 7:1598–1603CrossRefPubMed

Wiley SR, Schooley K, Smolak PJ, Din WS, Huang CP, Nicholl JK, Sutherland GR, Smith TD, Rauch C, Smith CA (1995) Identification and characterization of a new member of the TNF family that induces apoptosis. Immunity 3:673–682CrossRefPubMed

Wohlfahrt ME, Beard BC, Lieber A, Kiem HP (2007) A capsid-modified, conditionally replicating oncolytic adenovirus vector expressing TRAIL Leads to enhanced cancer cell killing in human glioblastoma models. Cancer Res 67:8783–8790CrossRefPubMed

Wu Z, Asokan A, Samulski RJ (2006) Adeno-associated virus serotypes: Vector toolkit for human gene therapy. Mol Ther 14:316–327CrossRefPubMed

Zaiss AK, Muruve DA (2008) Immunity to adeno-associated virus vectors in animals and humans: a continued challenge. Gene Ther 15:808–816CrossRefPubMed

Zhao L, Dong A, Gu J, Liu Z, Zhang Y, Zhang W, Wang Y, He L, Qian C, Qian Q, Liu X (2006) The antitumor activity of TRAIL and IL-24 with replicating oncolytic adenovirus in colorectal cancer. Cancer Gene Ther 13:1011–1022CrossRefPubMed

Titel: The efficacy of combination therapy using adeno-associated virus-TRAIL targeting to telomerase activity and cisplatin in a mice model of hepatocellular carcinoma
verfasst von: Yigang Wang
Fang Huang
Haibo Cai
Yumei Wu
Guoqing He
Wen-Song Tan
Publikationsdatum: 01.12.2010
Verlag: Springer-Verlag
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 12/2010
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-010-0841-8

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The efficacy of combination therapy using adeno-associated virus-TRAIL targeting to telomerase activity and cisplatin in a mice model of hepatocellular carcinoma

Abstract

Purpose

Methods

Results

Conclusions

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Springer Medizin

Abstract

Purpose

Methods

Results

Conclusions

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