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Mechanism and therapeutic prospect of resveratrol combined with TRAIL in the treatment of renal cell carcinoma
- Source :
- Cancer Gene Therapy. 27:619-623
- Publication Year :
- 2019
- Publisher :
- Springer Science and Business Media LLC, 2019.
-
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.
- Subjects :
- 0301 basic medicine
Cancer Research
Chemistry
Autophagy
Resveratrol
urologic and male genital diseases
medicine.disease
Ligand (biochemistry)
XIAP
03 medical and health sciences
chemistry.chemical_compound
030104 developmental biology
0302 clinical medicine
Renal cell carcinoma
In vivo
Apoptosis
030220 oncology & carcinogenesis
Cancer research
medicine
Molecular Medicine
Tumor necrosis factor alpha
Molecular Biology
Subjects
Details
- ISSN :
- 14765500 and 09291903
- Volume :
- 27
- Database :
- OpenAIRE
- Journal :
- Cancer Gene Therapy
- Accession number :
- edsair.doi...........92651966f69676d9d27536665af85f78