title: SIRT1 counteracted the activation of STAT3 and NF-κB to repress the gastric cancer growth.
abstract: Sirtuin-1 (SIRT1) possesses apparently dual roles in regulation of tumor. Previous reports have documented the crosstalk between SIRT1 with signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappa-B (NF-κB) signaling in leukemia, lymphoma and myeloma. In this study, the purpose was to survey the regulatory effects of SIRT1 on gastric cancer (GC) cells (AGS and MKN-45) and the relationships between SIRT1 and activation of STAT3 and NF-κB in GC cells. We found the SIRT1 activator (resveratrol RSV) contributed to the repression of viability and increase of senescence, which were rescued by SIRT1 inhibitor (nicotinamide NA) and SIRT1 depletion by CCK-8 assay and SA-β-gal assay respectively. Further study found SIRT1 activation (RSV supplement) not only inhibited the activation of STAT3 including STAT3 mRNA level, c-myc mRNA level phosphorylated STAT3 (pSTAT3) proteins and acetylizad STAT3 (acSTAT3) proteins, but also repression of pNF-κB p65 and acNF-κB p65. NA reversed the effects of RSV. In addition, either RSV or NA application could not change the cellular viability and senescence in MKN-45 cells with STAT3 knockdown or NF-κB knockdown. Overall, our findings suggested SIRT1 activation could induced the loss of viability and increases of senescence in GC in vitro. Moreover, our observations revealed SIRT1 displayed growth inhibitory activity in GC cells highly associated with causing repression of activation of STAT3 and NF-κB proteins via deacetylation.
authors: Department of Digestive Disease, Gansu Provincial Hospital 160 Donggang West Road, Lanzhou 730000, China.
authors: Juanjuan
authors: J
authors: Lu
authors: Department of Digestive Disease, Gansu Provincial Hospital 160 Donggang West Road, Lanzhou 730000, China.
authors: Liping
authors: L
authors: Zhang
authors: Department of Digestive Disease, Gansu Provincial Hospital 160 Donggang West Road, Lanzhou 730000, China.
authors: Xiang
authors: X
authors: Chen
authors: Department of Digestive Disease, Gansu Provincial Hospital 160 Donggang West Road, Lanzhou 730000, China.
authors: Qiming
authors: Q
authors: Lu
authors: Department of Digestive Disease, Gansu Provincial Hospital 160 Donggang West Road, Lanzhou 730000, China.
authors: Yuxia
authors: Y
authors: Yang
authors: Department of Digestive Disease, Gansu Provincial Hospital 160 Donggang West Road, Lanzhou 730000, China.
authors: Jingping
authors: J
authors: Liu
authors: Department of Digestive Disease, Gansu Provincial Hospital 160 Donggang West Road, Lanzhou 730000, China.
authors: Xin
authors: X
authors: Ma
keywords: NF-κB; STAT3; Sirtuin-1; acetylation; activation; gastric cancer