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Oncolytic adenovirus encoding tumor necrosis factor-related apoptosis inducing ligand (TRAIL) inhibits the growth and metastasis of triple-negative breast cancer
Authors:Wei Zhu  Hongwei Zhang  Yi Shi  Mangen Song  Bijun Zhu  Lai Wei
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
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.
Keywords:tumor necrosis factor-related apoptosis inducing ligand (TRAIL)  triple-negative breast cancer (TNBC)  adenovirus  virotherapy
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