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Mechanism and therapeutic prospect of resveratrol combined with TRAIL in the treatment of renal cell carcinoma

Cancer Gene Therapy volume 27, pages 619–623 (2020)Cite this article

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Abstract

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to kill a wide variety of tumor cells with minimal effects on normal cell. However, renal cell carcinoma (RCC) cells 786-0 and OS-RC-2 were resistant to TRAIL. The present study examines the potential of combining polyphenolic compound resveratrol (RES) with TRAIL. We found that RES can sensitize RCC cells to TRAIL-induced death. Electron microscopy analyses showed that RES plus TRAIL can induce both autophagy and apoptosis in RCC cells. It was proved that the apoptosis is caspase-dependent and the activation of caspase-8, caspase-9, and caspase-3 was involved in this process. Besides, we also found that XIAP expression was significantly inhibited after RES plus TRAIL treatment in RCC cells. Furthermore, a fiber-modified replication-deficient adenovirus Ad5/35-TRAIL was generated to test the synergistic effect of RES and TRAIL in vivo. Our data demonstrated that RES plus Ad5/35-TRAIL significantly inhibited RCC xenograft growth in nude mice. These results suggest the possibility of a new combination therapeutic leading to the improvement of RCC treatment.

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Acknowledgements

This work was supported by the National Natural Science Foundation of the People’s Republic of China (grant nos. 81760287, 31700763), Longyuan Youth Fund for Innovation and Entrepreneurship, Major Cultivation Projects in Central Colleges and Universities (31920190045) and Cultivation Project of Innovation Team in Central Colleges and Universities (31920190027) of Northwest Minzu University.

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Authors and Affiliations

  1. College of Animal Science and Technology, Jilin Provincial Engineering Research Center of Animal Probiotics, Key Lab of Animal Production, Product Quality and Security, Ministry of Education, Jilin Agricultural University, 130118, Changchun, China

    Yan Zeng, Chun-wei Shi & Xin Cao

  2. College of Life Science and Engineering, Center for Biomedical Research, Northwest Minzu University, 730030, Lanzhou, China

    Feng-di Li, Jiang-long Du, Yu-jia Xue & Xin Cao

  3. State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031, Shanghai, China

    Xin-yuan Liu & Na Wei

  4. Department of Molecular Medicine, The Scripps Research Institute, La Jolla, CA, 92037, USA

    Na Wei

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  1. Yan Zeng
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  2. Feng-di Li
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Correspondence to Xin Cao or Na Wei.

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Zeng, Y., Li, Fd., Shi, Cw. et al. Mechanism and therapeutic prospect of resveratrol combined with TRAIL in the treatment of renal cell carcinoma. Cancer Gene Ther 27, 619–623 (2020). https://doi.org/10.1038/s41417-019-0150-6

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  • DOI: https://doi.org/10.1038/s41417-019-0150-6

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