J Cancer 2015; 6(12):1214-1221. doi:10.7150/jca.12191

Research Paper

Expression Profiling Identifies Bezafibrate as Potential Therapeutic Drug for Lung Adenocarcinoma

Xinyan Liu1†, Xiaoqin Yang3†, Xinmei Chen4, Yantao Zhang2, Xuebin Pan2, Guiping Wang2✉, Yun Ye5 ✉

1. Magazine office, Guangzhou Medical University, Guangzhou 510182, P.R. China
2. Department of Pharmacy, College of Health sciences, Guangzhou Medical University, Guangzhou 510180, P.R. China
3. Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, P.R. China
4. Department of Biochemistry, School of Basic Science, Guangzhou Medical University, Guangzhou 510182, P.R. China
5. College of Biological and Chemical Engineering, Guangxi University of Science and Technology, Liuzhou 545006, P.R. China
† These authors contributed equally to this work.

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Liu X, Yang X, Chen X, Zhang Y, Pan X, Wang G, Ye Y. Expression Profiling Identifies Bezafibrate as Potential Therapeutic Drug for Lung Adenocarcinoma. J Cancer 2015; 6(12):1214-1221. doi:10.7150/jca.12191. Available from http://www.jcancer.org/v06p1214.htm

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Drug-induced gene expression patterns that invert disease profiles have recently been illustrated to be a new strategy for drug-repositioning. In the present study, we validated this approach and focused on prediction of novel drugs for lung adenocarcinoma (AC), for which there is a pressing need to find novel therapeutic compounds. Firstly, connectivity map (CMap) analysis computationally predicted bezafibrate as a putative compound against lung AC. Then this hypothesis was verified by in vitro assays of anti-proliferation and cell cycle arrest. In silico docking evidence indicated that bezafibrate could target cyclin dependent kinase 2(CDK2), which regulates progression through the cell cycle. Furthermore, we found that bezafibrate can significantly down-regulate the expression of CDK2 mRNA and p-CDK2. Using a nude mice xenograft model, we also found that bezafibrate could inhibit tumor growth of lung AC in vivo. In conclusion, this study proposed bezafibrate as a potential therapeutic option for lung AC patients, illustrating the potential of in silico drug screening.

Keywords: Lung adenocarcinoma, Connectivity map, Drug-repositioning, Bezafibrate