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01.12.2012 | Research | Ausgabe 1/2012 Open Access

World Journal of Surgical Oncology 1/2012

Gene expression profiling of the synergy of 5-aza-2-deoxycytidine and paclitaxel against renal cell carcinoma

Zeitschrift:
World Journal of Surgical Oncology > Ausgabe 1/2012
Autoren:
Tiandong Han, Donghao Shang, Xiuhong Xu, Ye Tian
Wichtige Hinweise

Electronic supplementary material

The online version of this article (doi:10.​1186/​1477-7819-10-183) contains supplementary material, which is available to authorized users.
Tiandong Han, Donghao Shang contributed equally to this work.

Competing interests

The authors declare that they have no competing interests.

Authors’ contributions

TH, DS conceived and designed the experiments. TH, XX performed the experiments. DS analyzed the data. DS, XX contributed reagents/materials/ analysis tools. TH, YT drafted the manuscript. All authors read and approved the final manuscript.

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.

Conclusion

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.
Zusatzmaterial
Additional file 1: DAC (A) and PTX (B, C) each caused dosage-dependent cell growth suppression of RCC cells. DAC (0.5 and 1 μM) increased the susceptibility of RCC cells to PTX (B for ACHN and C for NC 65 are shown). The combination of DAC and PTX caused synergistic growth suppression in all two RCC cell lines by isobolographic analysis (D). (DOC 332 KB)
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Additional file 2: Table S1 The top 10 up/down-regulated genes in the three different conditions normalized by untreated control.(JPEG 730 KB)
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Additional file 3: Table S2 The top 10 up/down-regulated synergy-related genes by DAC and PTX are shown in (A) and (B), and synergy-related pathways by DAC and/or PTX are shown in (C).(JPEG 734 KB)
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Authors’ original file for figure 1
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Authors’ original file for figure 2
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Authors’ original file for figure 3
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Literatur
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