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

Oncotarget
Juan QinXiao-Feng Zhu

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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Feb 17, 2019·Journal of Experimental & Clinical Cancer Research : CR·Yaoyong LuGong Zhang
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Datasets Mentioned

BETA
GSE59503

Methods Mentioned

BETA
flow cytometry
FACS
xenografts
transfection
PCR
xenograft
ubiquitination
protein assay
Assay

Software Mentioned

CalcuSyn

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