Identifying Differentially Expressed Genes and Screening Small Molecule Drugs for Lapatinib-resistance of Breast Cancer by a Bioinformatics Strategy
作者： Wen-Lei Zhuo , Liang Zhang , Qi-Chao Xie , Bo Zhu , Zheng-Tang Chen
DOI: 10.7314/APJCP.2014.15.24.10847
关键词: Gene expression 、 Small molecule 、 Actin cytoskeleton 、 Breast cancer 、 Biology 、 Bioinformatics 、 Epidermal growth factor receptor 、 Lapatinib 、 Cell 、 Tyrosine-kinase inhibitor
摘要: Background: Lapatinib, a dual tyrosine kinase inhibitor that interrupts the epidermal growth factor receptor (EGFR) and HER2/neu pathways, has been indicated to have significant efficacy in treating HER2-positive breast cancer. However, acquired drug resistance become very serious clinical problem hampers use of this agent. In study, we aimed screen small molecule drugs might reverse lapatinib-resistance cancer by exploring differentially expressed genes (DEGs) via bioinformatics method. Materials Methods: We downloaded gene expression profile BT474-J4 (acquired lapatinib-resistant) BT474 (lapatinib-sensitive) cell lines from Gene Expression Omnibus (GEO) database selected using dChip software. Then, ontology pathway enrichment analyses were performed with DAVID database. Finally, connectivity map was utilized for predicting potential chemicals lapatinib-resistance. Results: A total 1, 657 DEGs obtained. These enriched 10 including cycling, regulation actin cytoskeleton focal adhesion associate examples. addition, several molecules screened as therapeutic agents capable overcoming Conclusions: The results our analysis provided novel strategy investigating mechanism identifying treatment.
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