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已发表论文

GSK1838705A (一种类胰岛素的生长因子-1 受体/胰岛素受体抑制剂) 诱导细胞凋亡并能减少抗多西紫杉醇 (docetaxel) 的前列腺癌细胞在体外和体内存活力

 

Authors Zhou F, Chen X, Fan S, Tai S, Jiang C, Zhang Y, Hao Z, Zhou J, Shi H, Zhang L, Liang C

Published Date April 2015 Volume 2015:8 Pages 753—760

DOI http://dx.doi.org/10.2147/OTT.S79105

Received 11 December 2014, Accepted 14 February 2015, Published 10 April 2015

Abstract: Prostate cancer is the leading malignancy and the second most common cause of cancer-related death in men. Despite high cure rates with surgery and/or radiation, 30%–40% of patients eventually develop advanced cancer. Docetaxel is one of the most effective and well established chemotherapeutic agents for prostate cancer. However, docetaxel resistance often develops within months. Combination therapies have been proposed to improve the therapeutic efficacy of docetaxel in prostate cancer, and there is an urgent need to identify agents that are effective for treatment of the disease, especially docetaxel-resistant prostate cancer. In this work, we investigated the activity of GSK1838705A, a potent insulin-like growth factor-1 receptor (IGF1R)/insulin receptor (IR) inhibitor, in prostate cancer, especially docetaxel-resistant prostate cancer. We found that GSK1838705A could effectively reduce the viability of both docetaxel-sensitive and docetaxel-resistant prostate cancer cells. GSK1838705A induced marked apoptosis in docetaxel-resistant cells, and also dramatically inhibited migration of these cells. Further, GSK1838705A significantly inhibited phosphorylation of IGF1R/IR. Importantly, GSK1838705A significantly suppressed docetaxel-resistant PC-3R tumor growth in vivo. This is the first study of GSK1838705A in prostate cancer. Our results indicate that GSK1838705A is a promising compound for the treatment of prostate cancer, especially for those who develop resistance to docetaxel, and might shed new light on treatment for prostate cancer.
Keywords: prostate cancer, GSK1838705A, insulin-like growth factor-1 receptor/insulin receptor inhibitor, viability, resistance, migration






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