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Archive > Volume 23 Issue 2 > 2016,23(2):212-217. DOI:10.3872/j.issn.1007-385X.2016.02.010 Prev Next
Basic Research
Screening of candidate therapeutic compounds for colon cancer based on a pattern of gene expression profiles
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Abstract:
Objective:Gene expression profile is an important pattern to discover new uses of the existing drugs. Application value of the gene expression profile in screening of candidate drugs for colon cancer was discussed. Methods: First of all, data set of gene expression profile for colon cancer (No. GSE41258) was obtained from GEO data bank of PubMed. Fifty-three paired data of colon cancer and colonic mucosal tissues were selected from Memorial Sloan-Kettering Cancer Center of the United States, and their qualities analyzed with RMA express software. Then a gene expression profile for characteristics of colon cancer was established with Dchip software. Finally candidate compounds for therapy of colon cancer were screened by Connectivity Map (CMAP) and confirmed by experiments. Results: Thirty-six paired samples were selected through analysis of microarray chips for further research. A gene expression profile for characteristics of colon cancer was composed of 371 genes which include 94 up-regulation genes and 277 down-regulation genes. With analysis of CMAP, 10 candidate compounds, including vorinostat, tanespimycin (17-AAG) etc, were screened out, in which 17-AAG with high enrichment scores was selected for the validation. By the following experiments, it was confirmed that 17-AAG can effectively inhibit proliferation of colon cancer SW480 and HT29 cell lines. After treatment of 17-AAG for 24 and 48h, the IC50 values of SW480 cell line were 0.73 μmol/L and 0.41 μmol/L respectively, while the IC50 values of HT29 cell line was 0.72 μmol/L and 0.5 μmol/L respectively. Analysis of flow cytometry assay showed that 17-AAG could block cell cycle of the colon cancer cells at G1 phase. Conclusion: Multiple candidate therapeutic compounds for colon cancer were identified based on a pattern of gene expression profiles. A pattern of gene expression profiles might be of an important significance in screening of candidate drugs.
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Project Supported:
Project supported by the Program of Building Strong Traditional Chinese Medicine, Bureau of Traditional Chinese Medicine, Guangdong Province (No. 20121001)
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