Oncotarget

Research Papers:

DC120, a novel AKT inhibitor, preferentially suppresses nasopharyngeal carcinoma cancer stem-like cells by downregulating Sox2

Juan Qin _, Jiao Ji, Rong Deng, Jun Tang, Fen Yang, Gong-Kan Feng, Wen-Dan Chen, Xiao-Qi Wu, Xiao-Jun Qian, Ke Ding and Xiao-Feng Zhu

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Oncotarget. 2015; 6:6944-6958. https://doi.org/10.18632/oncotarget.3128

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Abstract

Juan Qin1,*, Jiao Ji1,*, Rong Deng1,*, Jun Tang1,2, Fen Yang1, Gong-Kan Feng1, Wen-Dan Chen1, Xiao-Qi Wu1, Xiao-Jun Qian1, Ke Ding3,4, Xiao-Feng Zhu1

1State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China

2Department of Breast Oncology, Sun Yat-sen University, Guangzhou, China

3Graduate School of Chinese Academy of Sciences, Beijing, China

4Key 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: [email protected]

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.


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