INTERNATIONAL CONGRESS OF
CancerGenetics
Resveratrol enhances sensitivity of renal cell carcinoma to tivozanib: an in-vitro study
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Helia Azodian Ghajar,1,*
1. Urology Research Center, Tehran University of Medical Sciences, Tehran Iran
- Introduction: Since tivozanib has many side effects in the treatment of kidney cancer, we decided to use resveratrol as a bioactive molecule with anticancer and antioxidant properties to make tivozanib more effective and also reduce its side effects in kidney cancer cell line.
- Methods: To determine IC50 levels, ACHN cells was exposed to different concentration of tivozanib and resveratrol. Our data indicated that IC50 values for tivozanib (0.5μM) and resveratrol (30μM) with MTT in a dose and time-dependent manner. Due to the efficacy of resveratrol in combination with tivozanib, we used 20μM resveratrol, and 0.25μM tivozanib instead of 30μM and 0.25μM respectively. This data was approved by flow cytometry for ACHN cell line with 38.39, 14.74 and 66.06 percent apoptosis and 8.25, 5.12 and 15.6 percent subG1 for tivozanib, resveratrol and tivozanib-resveratrol combination respectively which was as a consequence of cell cycle arrest at G1/S phase. The treatment also reduced cells’ migration, fragmented nuclei, 3D spheroid and colony formation potentials in analyses. Evaluation of gene expression presented that the effect of the tivozanib and resveratrol combination in ACHN cell lines is completely different during the evaluation of apoptosis genes, BAX, P53 genes and E-Cadherin had significantly increased expression compared to single treatment groups (P < 0.01). Meanwhile, a significant decrease was observed in the expression of VEGFC and HIF1α genes in the combination group compared to the monotherapy groups (P < 0.001).
- Results: In this in vitro study, we evaluated the effect of tivozanib, resveratrol and tivozanib- resveratrol combination therapy in ACHN cell line as representatives of human kidney cancer. The assessment includes Hoechst dye staining, scratch-wound assay, 3D spheroid, 2D colony formation assay, flow cytometric analysis of apoptosis and DNA cell cycle, real-time PCR (BAX/BCL2, E-cadherin, Snail, HIF1(, VEGFC and KLK3 genes).
- Conclusion: this study shows that resveratrol, an active phytochemical, increases the sensitivity of renal cell carcinoma cells to tivozanib by reducing the survival of renal cancer cells, suppressing the proliferation, migration, colonization and spheroid formation and decreasing VEGFC/ HIF-1α expression. In the combined group, resveratrol led to a decrease in the dose of tivozanib. Our results suggest that resveratrol combined with tivozanib may be a new therapeutic strategy and an optimal choice for renal cell carcinoma.
- Keywords: Tivozanib, Resveratrol, Prostate cancer, Combination therapy
