Gene expression profiling of the synergy of decitabine and paclitaxel against renal cell carcinoma

HAN Tiandong; SHANG Donghao; XU Xiuhong; TIAN Ye

Abstract：Objective To investigate the gene transcriptional alteration and search for possible molecular mechanism and pathways implicated in the synergy of DAC and PTX against renal cell caroinoma( RCC) . Methods cDNA microarray was performed and coupled with real-time PCR to identify critical genes in the synergistic mechanism of both agents against RCC cells( ACHN and NC 65) . Various patterns of gene expression were observed by cluster analysis. IPA software was used to analyze possible biological path-ways and explore the inter-relationships between interesting network genes. Suppression of PI3K/Akt pathway by DAC and/or PTX was clarified by Western blotting. Results Several key regulatory genes were identified and confirmed, such as lymphoid enhancer factor 1, transforming growth factor β induced gene, C-X-C motif ligand 5 and myelocytomatosis viral related oncogene, and they may play a pivotal role in the synergy of DAC and PTX. The PI3K/Akt, amb2 Integrin, IL2-mediated and IL23-mediated pathways include in the synergy of DAC and PTX against RCC. Moreover, 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. Conclusion The activation of PI3K/Akt pathway and other genes may participate in the synergy of two agents. The PI3K/Akt pathway could be suppressed synergistically by two agents.