Jianxin Chen1, Yifen Wu1, Shuji Li2, Hongyuan Wu3, Libo Li1. 1. Dongguan People's Hospital Affiliated to Southern Medical University, Dongguan 523059, China; Department of Basic Medical Sciences. 2. Department of Health Management, Nanfang Hospital. 3. Southern Medical University, Guangzhou 510515, China.
Abstract
OBJECTIVE: To study the inhibitory effect of 10-gingerol on the proliferation of hepatocellular carcinoma HepG2 cells and the role of Src/STAT3 signaling pathway in mediating the effect. METHODS: SYBYL-X2.1 software was used to simulate the interaction between 10-gingerol and Src. HepG2 cells treated with 10-gingerol at 1, 3, 10 or μol/L for 24 h were assessed for cell viability using MTT assay, and EdU staining was used to detect the cell proliferation and calculate the number of positive cells. The expressions of p-Src and p-STAT3 were detected using Western blotting, and the mRNA expressions of the target genes of STAT3 (cyclin D1 and CMCC) were detected using qPCR. RESULTS: 10-gingerol was capable of forming hydrogen bond with such Src residues as TRY-340, MET-341, MET-314, ASP-404, and ILE-336. MTT assay showed that 10-gingerol at 3 and 10 μmol/L significantly lowered the viability of HepG2 cells (P < 0.001). Treatment with 1, 3, and 10 μmol/L 10-gingerol significantly reduces the number of EdU-positive HepG 2 cells (P < 0.001). Western blotting showed that 10-gingerol at 3 and 10 μmol/L significantly decreased the phosphorylation levels of Src and STAT3 in HepG2 cells (P < 0.01). 10-gingerol at 1, 3, and 10 μmol/L significantly decreased the mRNA expressions of cyclin D1 and CMCC as shown by qPCR (P < 0.01). CONCLUSIONS: 10-gingerol can dose-dependently inhibit the proliferation of HepG2 cells and suppress the activation of Src and STAT3.
OBJECTIVE: To study the inhibitory effect of 10-gingerol on the proliferation of hepatocellular carcinoma HepG2 cells and the role of Src/STAT3 signaling pathway in mediating the effect. METHODS: SYBYL-X2.1 software was used to simulate the interaction between 10-gingerol and Src. HepG2 cells treated with 10-gingerol at 1, 3, 10 or μol/L for 24 h were assessed for cell viability using MTT assay, and EdU staining was used to detect the cell proliferation and calculate the number of positive cells. The expressions of p-Src and p-STAT3 were detected using Western blotting, and the mRNA expressions of the target genes of STAT3 (cyclin D1 and CMCC) were detected using qPCR. RESULTS:10-gingerol was capable of forming hydrogen bond with such Src residues as TRY-340, MET-341, MET-314, ASP-404, and ILE-336. MTT assay showed that 10-gingerol at 3 and 10 μmol/L significantly lowered the viability of HepG2 cells (P < 0.001). Treatment with 1, 3, and 10 μmol/L 10-gingerol significantly reduces the number of EdU-positive HepG 2 cells (P < 0.001). Western blotting showed that 10-gingerol at 3 and 10 μmol/L significantly decreased the phosphorylation levels of Src and STAT3 in HepG2 cells (P < 0.01). 10-gingerol at 1, 3, and 10 μmol/L significantly decreased the mRNA expressions of cyclin D1 and CMCC as shown by qPCR (P < 0.01). CONCLUSIONS:10-gingerol can dose-dependently inhibit the proliferation of HepG2 cells and suppress the activation of Src and STAT3.
Authors: Kathryn A O'Donnell; Vincent W Keng; Brian York; Erin L Reineke; Daekwan Seo; Danhua Fan; Kevin A T Silverstein; Christina T Schrum; Wei Rose Xie; Loris Mularoni; Sarah J Wheelan; Michael S Torbenson; Bert W O'Malley; David A Largaespada; Jef D Boeke Journal: Proc Natl Acad Sci U S A Date: 2012-05-03 Impact factor: 11.205
Authors: Lindsey A Torre; Freddie Bray; Rebecca L Siegel; Jacques Ferlay; Joannie Lortet-Tieulent; Ahmedin Jemal Journal: CA Cancer J Clin Date: 2015-02-04 Impact factor: 508.702
Authors: Harry P Selker; John B Buse; Robert M Califf; Robert Carter; Dan M Cooper; Jonathan Davis; Daniel E Ford; Pietro Galassetti; Lisa Guay-Woodford; Gordon S Huggins; Amanda Kasper; Karl Kieburtz; Aaron Kirby; Andreas K Klein; Joel Kline; Robert T O' Neill; Marie Rape; Douglas J Reichgott; Svetlana Rojevsky; Gary E Rosenthal; Eric P Rubinstein; Amy Shepherd; Mark Stacy; Norma Terrin; Mark Wallace; Lisa Welch Journal: Clin Transl Sci Date: 2015-07-16 Impact factor: 4.689