DC120, a novel AKT inhibitor, preferentially suppresses nasopharyngeal carcinoma cancer stem-like cells by downregulating Sox2.
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.
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Juan
J
Qin
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Jiao
J
Ji
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Rong
R
Deng
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.|Department of Breast Oncology, Sun Yat-sen University, Guangzhou, China.
Jun
J
Tang
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Fen
F
Yang
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Gong-Kan
GK
Feng
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Wen-Dan
WD
Chen
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Xiao-Qi
XQ
Wu
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Xiao-Jun
XJ
Qian
Graduate School of Chinese Academy of Sciences, Beijing, China.|Key Laboratory of Regenerative Biology and Institute of Chemical Biology, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou China.
Ke
K
Ding
State Key Laboratory of Oncology in South China, Cancer Center, Sun Yat-sen University, Guangzhou, China.
Xiao-Feng
XF
Zhu
D000255:Adenosine Triphosphate / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry; D001665:Binding Sites; D002277:Carcinoma; D002469:Cell Separation; D015536:Down-Regulation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D016513:Mice, SCID; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000201:enzymology*; D009364:Neoplasm Recurrence, Local; D014411:Neoplastic Stem Cells / Q000187:drug effects*; D010641:Phenotype; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry*; D055748:SOXB1 Transcription Factors / Q000378:metabolism*; D013844:Thiazoles / Q000737:chemistry*; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; C575445:N-(1-amino-3-(2,4-dichlorophenyl)propan-2-yl)-2-(2-(methylamino)pyrimidin-4-yl)thiazole-5-carboxamide; D011743:Pyrimidines; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D013844:Thiazoles; D000255:Adenosine Triphosphate; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3
DC120; PKB/AKT; cancer stem-like cells; nasopharyngeal carcinoma