title: Gene expression profiling of the synergy of 5-aza-2'-deoxycytidine and paclitaxel against renal cell carcinoma.
abstract: BACKGROUND
  Renal 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.
  
  
  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. 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.
  
  
  RESULTS
  We 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Urology, Beijing Friendship Hospital, Capital Medical University, 95 Yong-An Road, Beijing 100050, China.
authors.forename: Tiandong
authors.initials: T
authors.lastname: Han
authors.forename: Donghao
authors.initials: D
authors.lastname: Shang
authors.forename: Xiuhong
authors.initials: X
authors.lastname: Xu
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001374:Azacitidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D000077209:Decitabine; D004357:Drug Synergism; D020869:Gene Expression Profiling; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D017239:Paclitaxel / Q000008:administration & dosage; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D000077209:Decitabine; D001374:Azacitidine; D017239:Paclitaxel