Abstract
BackgroundRenal cell carcinoma (RCC) is one of the most common kidney cancers and is highly resistant to chemotherapy. We previously demonstrated that 5-aza-2′-deoxycytidine (DAC) could significantly increase the susceptibility of renal cell carcinoma (RCC) cells to paclitaxel (PTX) treatment in vitro, and showed the synergy of DAC and PTX against RCC. The purpose of this study is to investigated the gene transcriptional alteration and investigate possible molecular mechanism and pathways implicated in the synergy of DAC and PTX against RCC.MethodscDNA microarray was performed and coupled with real-time PCR to identify critical genes in the synergistic mechanism of both agents against RCC cells. Various patterns of gene expression were observed by cluster analysis. IPA software was used to analyze possible biological pathways and to explore the inter-relationships between interesting network genes.ResultsWe found that lymphoid enhancer-binding factor 1 (LEF1), transforming growth factor β-induced (TGFBI), C-X-C motif ligand 5 (CXCL5) and myelocytomatosis viral related oncogene (c-myc) may play a pivotal role in the synergy of DAC and PTX. The PI3K/Akt pathway and other pathways associated with cyclins, DNA replication and cell cycle/mitotic regulation were also associated with the synergy of DAC and PTX against RCC.ConclusionThe activation of PI3K/Akt-LEF1/β-catenin pathway could be suppressed synergistically by two agents and that PI3K/Akt-LEF1/β-catenin pathway is participated in the synergy of two agents.
Highlights
Renal cell carcinoma (RCC) is one of the most common kidney cancers and is highly resistant to chemotherapy
We investigated the basic mechanism of the synergy of DAC and PTX against RCC cells; DAC inhibited cell growth by the induction of G2/M cell cycle arrest, and the effect of PTX depended on apoptosis induction and G2/M cell cycle arrest
Results cDNA microarray and cluster analysis Scanning images of cDNA microarray are displayed in Figure 1A and 1B, Cy3 stands for the controls, whereas Cy5 stands for treatment with DAC, PTX or DAC + PTX
Summary
Renal cell carcinoma (RCC) is one of the most common kidney cancers and is highly resistant to chemotherapy. The landscape for RCC treatment has changed dramatically in recent years, vascular endothelial growth might be attributed to its inhibition of DNA methylation and activation of cell cycle checkpoint signaling, to previous reports for DNA repair responses [10,11]. These two activities may not be entirely independent of each other given that the expression of some genes involved in cell cycle regulation is epigenetically controlled
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