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// Juan Qin 1, * , Jiao Ji 1, * , Rong Deng 1, * , Jun Tang 1, 2 , Fen Yang 1 , Gong-Kan Feng 1 , Wen-Dan Chen 1 , Xiao-Qi Wu 1 , Xiao-Jun Qian 1 , Ke Ding 3, 4 , Xiao-Feng Zhu 1 1 State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China 2 Department of Breast Oncology, Sun Yat-sen University, Guangzhou, China 3 Graduate School of Chinese Academy of Sciences, Beijing, China 4 Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou China * These authors have contributed equally to this work Correspondence to: Xiao-Feng Zhu, e-mail: zhuxfeng@mail.sysu.edu.cn Keywords: DC120, PKB/AKT, nasopharyngeal carcinoma, cancer stem-like cells Received: December 12, 2014 Accepted: January 09, 2015 Published: February 04, 2015 ABSTRACT Side population (SP) contains cancer stem-like cells (CSLCs). In this study, we characterized SP cells from nasopharyngeal carcinoma (NPC) cell lines and found that SP cells had a higher self-renewal ability in vitro and greater tumorigenicity in vivo . The AKT pathway was activated in NPC SP cells. DC120, a 2-pyrimidyl-5-amidothiazole inhibitor of the ATP binding site of AKT, inhibited phosphorylation of FKHRL1 and GSK-3β. DC120 inhibited SP fraction, the sphere-forming ability in vitro and growth of primary xenografts as well as secondary xenografts' tumor recurrence. This inhibition was accompanied by reduced expression of stem-related gene Sox2 due to induction of p27 and miR-30a. A combination of DC120 and CDDP more effectively inhibited NPC cells compared with monotherapy in vitro and in vivo . Clinical evaluation of DC120 is warranted. |
