title: FoxP3 inhibits proliferation and induces apoptosis of gastric cancer cells by activating the apoptotic signaling pathway.
abstract: Forkhead Box Protein 3 (FoxP3) was identified as a key transcription factor to the occurring and function of the regulatory T cells (Tregs). However, limited evidence indicated its function in tumor cells. To elucidate the precise roles and underlying molecular mechanism of FoxP3 in gastric cancer (GC), we examined the expression of FoxP3 and the consequences of interfering with FoxP3 gene in human GC cell lines, AGS and MKN45, by multiple cellular and molecular approaches, such as immunofluorescence, gene transfection, CCK-8 assay, clone formation assay, TUNEL assay, Flow cytometry, immunoassay and quantities polymerase chain reaction (PCR). As a result, FoxP3 was expressed both in nucleus and cytoplasm of GC cells. Up-regulation of FoxP3 inhibited cell proliferation and promoted cell apoptosis. Overexpression of FoxP3 increased the protein and mRNA levels of proapoptotic molecules, such as poly ADP-ribose polymerase1 (PARP), caspase-3 and caspase-9, and repressed the expression of antiapoptotic molecules, such as cellular inhibitor of apoptosis-1 (c-IAP1) and the long isoform of B cell leukemia/lymphoma-2 (Bcl-2). Furthermore, silencing of FoxP3 by siRNA in GC cells reduced the expression of proapoptotic genes, such as PARP, caspase-3 and caspase-9. Collectively, our findings identify the novel roles of FoxP3 in inhibiting proliferation and inducing apoptosis in GC cells by regulating apoptotic signaling, which could be a promising therapeutic approach for gastric cancer.
authors.affiliation: Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai, China.
authors.forename: Gui-Fen
authors.initials: GF
authors.lastname: Ma
authors.forename: Shi-Yao
authors.initials: SY
authors.lastname: Chen
authors.forename: Zhi-Rong
authors.initials: ZR
authors.lastname: Sun
authors.forename: Qing
authors.initials: Q
authors.lastname: Miao
authors.forename: Yi-Mei
authors.initials: YM
authors.lastname: Liu
authors.forename: Xiao-Qing
authors.initials: XQ
authors.lastname: Zeng
authors.forename: Tian-Cheng
authors.initials: TC
authors.lastname: Luo
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Ma
authors.forename: Jing-Jing
authors.initials: JJ
authors.lastname: Lian
authors.forename: Dong-Li
authors.initials: DL
authors.lastname: Song
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology*; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D051858:Forkhead Transcription Factors / Q000235:genetics; D006801:Humans; D024101:Mitochondrial Proteins / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology*; D015854:Up-Regulation
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D020169:Caspases