J Cancer 2017; 8(12):2256-2262. doi:10.7150/jca.19566
Development of a new analog of SGK1 inhibitor and its evaluation as a therapeutic molecule of colorectal cancer
1. Regeneration and Ageing Lab, School of Life Science, Shanghai University, Shanghai 200444, China
2. Department of Chemistry, Qianweichang College, Innovative Drug Research Center, Shanghai University, Shanghai 200444, China
3. Department of General Surgery, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
4. Department of Cardiology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, China
#These authors contributed equally to this work.
Colorectal cancer (CRC) is one of the most leading causes of cancer-related death worldwide. The serum and glucocorticoid inducible kinase SGK1 is highly expressed and involved in several tumors. GSK650394, a SGK1 inhibitor, has been proved to be effective in impeding tumor growth in vitro. In this study, we developed a novel analog of GSK650394, and evaluated its effects on CRC cells and tumor growth both in vitro and in vivo. HCT116 cells were treated with a concentration gradient of new developed compounds and cholecystokinin octapeptide (CCK-8) assay was used to calculate the IC50 value of every analog. Cell proliferation analysis was estimated from EdU staining and flow cytometry in vitro, and immunohistochemistry of Ki67 and PCNA in vivo. Cell migration analysis was examined using the transwell assay. In vivo tumor growth was determined in athymic nude mice by injecting the HCT116 cells in the subcutaneous tissue, followed by the injection of QGY-5-114-A. We found that new developed GSK650394 analog QGY-5-114-A has lower IC50 value, and treatment with QGY-5-114-A significantly inhibited CRC cell proliferation and migration in vitro. Besides that, colonic tumor growth was also dramatically restricted by QGY-5-114-A in vivo. In conclusion, pharmacological treatment with QGY-5-114-A impedes CRC tumor cell proliferation, migration and tumor growth.
Keywords: Colorectal cancer, Serum and glucocorticoid inducible kinase 1, Inhibitor, Cell proliferation, Cell migration, Colonic tumor growth
Liang X, Lan C, Zhou J, Fu W, Long X, An Y, Jiao G, Wang K, Li Y, Xu J, Huang Q, Xu B, Xiao J. Development of a new analog of SGK1 inhibitor and its evaluation as a therapeutic molecule of colorectal cancer. J Cancer 2017; 8(12):2256-2262. doi:10.7150/jca.19566. Available from http://www.jcancer.org/v08p2256.htm