Oncolytic adenovirus encoding tumor necrosis factor-related apoptosis inducing ligand (TRAIL) inhibits the growth and metastasis of triple-negative breast cancer |
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Authors: | Wei Zhu Hongwei Zhang Yi Shi Mangen Song Bijun Zhu Lai Wei |
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Institution: | 1.Department of General Surgery; Zhongshan Hospital; Fudan University, Shanghai, PR China;2.Experimental Center; Zhongshan Hospital; Fudan University; Shanghai, PR China;3.Department of Cardiac Surgery; Zhongshan Hospital; Fudan University; Shanghai, PR China |
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Abstract: | Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising cancer therapeutic target due to its selective apoptosis-inducing effect in cancer cells. To efficiently deliver TRAIL to the tumor cells, an oncolytic adenovirus (p55-hTERT-HRE-TRAIL) carrying the TRAIL coding sequence was constructed. In the present study, we aimed to investigate the effect of p55-hTERT-HRE-TRAIL on the growth and metastasis of triple-negative breast cancer (TNBC). We observed that infection of the recombinant adenovirus resulted in expression of TRAIL and massive cell death in a TNBC cell line MDA-MB-231. This effect is much weaker in MCF-10A, which is a normal breast cell line. Administration of P55-HTERT-HRE-TRAIL significantly reduced orthotopic breast tumor growth and extended survival in a metastatic model. Our results suggest the oncolytic adenovirus armed with P55-HTERT-HRE-TRAIL, which exhibited enhanced anti-tumor activity and improved survival, is a promising candidate for virotherapy of TNBC. |
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Keywords: | tumor necrosis factor-related apoptosis inducing ligand (TRAIL) triple-negative breast cancer (TNBC) adenovirus virotherapy |
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