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.
Cancer gene therapy. 2019 Oct 30 [Epub ahead of print]
Yan Zeng, Feng-di Li, Chun-Wei Shi, Jiang-Long Du, Yu-Jia Xue, Xin-Yuan Liu, Xin Cao, Na Wei
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., College of Life Science and Engineering, Center for Biomedical Research, Northwest Minzu University, 730030, Lanzhou, China., State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031, Shanghai, China., 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. ., State Key Laboratory of Cell Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 200031, Shanghai, China. .