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Proteomic analysis of cell cycle arrest and differentiation induction caused by ATPR, a derivative of all-trans retinoic acid, in human gastric cancer SGC-7901 cells

ABSTRACT: Experimental design: Peptides digested from the total cellular proteins were analyzed by reverse phase LC–MS/MS followed by a label-free quantification analysis. The SEQUEST search engine was used to identify proteins and bioinformatics resources were used to investigate the involved pathways for the differentially expressed proteins. Results: 13 down-regulated proteins were identified in the ATPR-treated group. Bioinformatics analysis showed that the effects of ATPR on 14-3-3 might potentially involve the PI3K-AKT-FOXO pathway and P27Kip1 expression. Western blot and RT-PCR analysis showed that ATPR could inhibit AKT phosphorylation, up-regulate the expression of FOXO1A and P27Kip1 at both the protein and mRNA levels, and down-regulate the cytoplasmic expression of cyclin E and CDK2. ATPR-induced G0/G1 phase arrest and differentiation can be ablated if the P27kip1 gene is silenced with sequence-specific siRNA. Conclusions and clinical relevance: ATPR might cause cell cycle arrest and differentiation in SGC-7901 cells by simultaneously inhibiting the phosphorylation of AKT and down-regulating 14-3-3. This change would then enhance the inhibition of cyclin E/CDK2 by up-regulating FOXO1A and P27Kip1. Our findings could be of value for finding new drug targets and for developing more effective differentiation inducer.

INSTRUMENT(S): LTQ Orbitrap

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Cell Culture, Gastric Gland

DISEASE(S): Gastric Adenocarcinoma

SUBMITTER: Xia Quan

LAB HEAD: Quan Xia

PROVIDER: PXD005605 | Pride | 2017-02-13

REPOSITORIES: Pride

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Proteomic analysis of cell cycle arrest and differentiation induction caused by ATPR, a derivative of all-trans retinoic acid, in human gastric cancer SGC-7901 cells.

Xia Quan Q Zhao Yingli Y Wang Jiali J Qiao Wenhao W Zhang Dongling D Yin Hao H Xu Dujuan D Chen Feihu F

Proteomics. Clinical applications 20170306 7-8

<h4>Purpose</h4>4-amino-2-trifluoromethyl-phenyl retinate (ATPR) was reported to potentially inhibit proliferation and induce differentiation activity in some tumor cells. In this study, a proteomics approach was used to investigate the possible mechanism by screening the differentially expressed protein profiles of SGC-7901 cells before and after ATPR-treatment in vitro.<h4>Experimental design</h4>Peptides digested from the total cellular proteins were analyzed by reverse phase LC-MS/MS followe ...[more]

PMID: 28164444

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	ATPR-1.raw	Raw
	ATPR-2.prot.xml	Xml
	ATPR-2.raw	Raw
	ATPR-3.prot.xml	Xml