Radiotherapy Sensitization by Tumor-Specific <i>TRAIL</i> Gene Targeting Improves Survival of Mice Bearing Human Non–Small Cell Lung Cancer

Zhang, Xiaochun; Cheung, R.; Komaki, Ritsuko; Fang, Bingliang; Chang, Joe Y.

doi:10.1158/1078-0432.ccr-04-2699

Cited by 36 publications

(24 citation statements)

References 44 publications

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“…This limitation can be overcome by sensitizing cancer cells to TRAIL using cytotoxic chemotherapeutic drugs or ionizing radiation. [41][42][43] We have previously observed that cultured thoracic cancer cells, while expressing adequate levels of DR4/ DR5, are generally refractory to the cytotoxic effect of the soluble recombinant death ligand Apo2L/TRAIL. [21][22][23] Infecting these cells with AdVgTRAIL caused at most moderate reduction of cell viability at an MOI of 10 PFU per cell.…”

Section: Discussionmentioning

confidence: 99%

“…[38][39][40] As a matter of fact, this construct has significant anticancer property with no apparent hepatotoxicity 40 when administered intravenously in animals bearing human xenografts and its tumoricidal activity is potentiated by combination with cytotoxic chemotherapy or ionizing radiation. [41][42][43] Moreover, the TRAIL gene therapy efficiently mediates apoptosis even in TRAILrefractory cells, 39,44 making it an attractive alternative to recombinant TRAIL receptor ligands. Nguyen et al 45 previously reported that pretreatment of cultured cancer cells with subtherapeutic concentrations of the chemotherapeutic drug cisplatin (CDDP) resulted in enhancement of adenoviral transgene expression (either the reporter gene b-galactosidase gene (LacZ) or the therapeutic gene p53 under the control of the cytomegalovirus (CMV) promoter/enhancer), via a yet to be defined mechanism.…”

Section: Introductionmentioning

confidence: 99%

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Cisplatin enhances the antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand gene therapy via recruitment of the mitochondria-dependent death signaling pathway

et al. 2008

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Despite adequately expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4/DR5, malignant cells are frequently refractory to the cytotoxic effect of this apoptosis-inducing ligand. The susceptibility of cancer cells to TRAIL can be potentiated by cisplatin (CDDP). This study was designed to evaluate the ability of cisplatin to enhance the cytotoxic effect of TRAIL gene therapy using the recombinant adenovirus-mediated tumor-selective expression of membrane-bound green fluorescence protein (GFP)-TRAIL fusion protein (AdVgTRAIL) on thoracic cancer cells and to elucidate the putative mechanisms responsible for this synergistic combination effect. While causing little death of cultured thoracic cancer cells by itself, AdVgTRAIL in combination with CDDP, on the other hand, mediated profound supra-additive cytotoxicity and apoptosis via a strong bystander effect. CDDP/AdVgTRAIL-induced cytotoxicity was completely abrogated either by the pancaspase inhibitor zVAD-fmk or by the selective caspase 9 inhibitor or by transient knockdown of caspase 9 by siRNA, indicating that this process was caspase-mediated and mitochondria-dependent. This was confirmed by the observation that Bcl2 overexpression protected the cells from combinationinduced cytotoxicity. Robust activation of caspase 8 activity in combination-treated cells was blocked by overexpression of Bcl2, indicating that caspase 8 activation was secondary to the mitochondria-mediated amplification feedback loop. Combining CDDP with AdVgTRAIL greatly enhances its tumoricidal efficacy in cultured thoracic cancer cells in vitro. The two agents interact to mediate profound activation of caspase cascade via recruitment of the mitochondria and positive feedback loop. The CDDP/ AdVgTRAIL combination also exhibits a strong antitumor effect in in vivo animal model of human cancer xenografts.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cisplatin enhances the antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand gene therapy via recruitment of the mitochondria-dependent death signaling pathway

et al. 2008

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“…14,[43][44][45][46] Another major concern of toxicity is the potential ischemic and hemorrhagic reaction in normal tissues. 47,48 In order to minimize these potential side effects and restrict the expression of TRAIL in the cancer cells, we selected the hTERT promoter as a cancer specific promoter. In the present study, we have shown that the hTERT promoter selectively mediated the expression of TRAIL in SACC-83 tumor cells (Figs.…”

Section: Application Of Gene Therapy In the Adenoid Cystic Carcinomamentioning

confidence: 99%

Adenoviral mediated transduction of adenoid cystic carcinoma by human TRAIL gene driven with hTERT tumor specific promoter induces apoptosis

Zang¹,

Miao²,

Mu³

et al. 2009

Cancer Biology & Therapy

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“…15,16 Recent researches to improve the clinical outcome in such patients include altered irradiation fraction schedule and the introduction of chemotherapy, biotherapy, immunotherapy, virotherapy, or gene therapy on a concurrent or adjuvant basis. [17][18][19][20][21][22] Survivin gene expression has been identified in a majority of NSCLC. 3 Additionally, Tamm et al 23 reported that among all the human tumor cells screened, lung cancer cells expressed the highest levels of survivin.…”

Section: Introductionmentioning

confidence: 99%

Adenovirus-mediated transfer of siRNA against survivin enhances the radiosensitivity of human non-small cell lung cancer cells

Yang

Weng

et al. 2009

Cancer Gene Ther

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Expression of survivin has been reported to be correlated with shorter survival in patients with non-small cell lung cancer (NSCLC), and overexpression of survivin may lead to radioresistance in various human cancers. In this study, we inhibited survivin expression by using an adenoviral vector (AdsiSurvivin)-mediated RNA interference to elucidate the combined effect of survivin-targeting gene therapy and radiotherapy on the NSCLC cells. Our data showed that AdsiSurvivin exerted survivin gene silencing, induced apoptosis, and significantly attenuated the growth potential in NSCLC cells within 72 h after infection. The combined treatment modalities with AdsiSurvivin infection and radiation were significantly more potent on cell-growth inhibition than monotherapy. In H1650, H460, A549, and H1975 human NSCLC cells, the survival ratios of AdsiSurvivin-treated groups at multiplicity of infection of 25 and 50 were significantly lower than those of control groups at varying radiation dose (0-8 Gy; three-way analysis of variance, Po0.05). The cytotoxicity of combined AdsiSurvivin infection and irradiation increased in a dose-dependent manner in both the virus and the irradiation treatment. Knockdown of the survivin gene expression seems to be a promising treatment strategy for NSCLC. Our data warrant the need for further effort to develop survivin-targeted radiosensitizer for lung cancer treatment.

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Radiotherapy Sensitization by Tumor-Specific TRAIL Gene Targeting Improves Survival of Mice Bearing Human Non–Small Cell Lung Cancer

Abstract: Purpose: To sensitize non^small cell lung cancer (NSCLC) to radiotherapy by tumor-specific

Cited by 36 publications

References 44 publications

Cisplatin enhances the antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand gene therapy via recruitment of the mitochondria-dependent death signaling pathway

Cisplatin enhances the antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand gene therapy via recruitment of the mitochondria-dependent death signaling pathway

Adenoviral mediated transduction of adenoid cystic carcinoma by human TRAIL gene driven with hTERT tumor specific promoter induces apoptosis

Adenovirus-mediated transfer of siRNA against survivin enhances the radiosensitivity of human non-small cell lung cancer cells

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