OBJECTIVETo 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.

METHODSSYBYL-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.

RESULTS10-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 ( < 0.001). Treatment with 1, 3, and 10 μmol/L 10-gingerol significantly reduces the number of EdU-positive HepG 2 cells ( < 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 ( < 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 ( < 0.01).

CONCLUSIONS10-gingerol can dose-dependently inhibit the proliferation of HepG2 cells and suppress the activation of Src and STAT3.