BACKGROUND Histone acetylation and DNA methylation are important mammalian epigenetic modifications that participate in the regulation of gene expression. Because dysregulation of histone deacetylase and DNA methyltransferases are hallmarks of malignancy, they have become promising therapeutic targets. In this study, we explored the anti-tumor activity of valproic acid (VPA), a histone deacetylase inhibitor (HDACi) and 5-Aza-2'-deoxycytidine (5-Aza), an inhibitor of DNA methyltransferases, on renal cell carcinoma (RCC) cell lines 786-O and 769-P. MATERIAL AND METHODS The cell proliferation was detected by xCELLigence RTCA DP Instrument, viability by CCK8 assay, cell apoptosis and cell cycle by flow cytometry, and cell migration by wound healing assay, Transwell assay and xCELLigence RTCA DP Instrument. RESULTS We discovered that VPA and 5-Aza could individually induce decreased viability and have an inhibitory effect on the proliferation of 786-O and 769-P cells. This anti-growth effect was more pronounced when the cells were treated with both VPA and 5-Aza. The combination of VPA and 5-Aza also elicited more apoptosis and produced more cell cycle arrest in the G1 phase for both cell lines. On the other hand, treatment of RCC cells with VPA, 5-Aza, or a combination of both resulted in slow wound healing and impaired migration. CONCLUSIONS These findings clearly demonstrated that VPA combined with 5-Aza could significantly increase anti-RCC effects by inhibiting cellular proliferation, inducing apoptosis, promoting cell cycle arrest and prohibiting the migration of human RCC cells.
Medical science monitor : international medical journal of experimental and clinical research. 2018 Feb 19*** epublish ***
Wenjin Xi, Xu Chen, Jinbo Sun, Wei Wang, Yi Huo, Guoxu Zheng, Jieheng Wu, Yufang Li, Angang Yang, Tao Wang
State Key Laboratory of Cancer Biology, Department of Immunology, Fourth Military Medical University, Xi'an, Shaanxi, China (mainland)., Department of Urology, Tangdu Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China (mainland)., Nuclear Medicine Diagnostic Center, Shaanxi Provincial Peple's Hospital, Xi'an, Shaanxi, China (mainland)., Department of Medical Genetics and Developmental Biology, Fourth Military Medical University, Xi'an, Shaanxi, China (mainland).