Abstract: Objective The aim of this study was to investigate the inhibitory effect of dihydroactinidiolide(DHAc)on proliferation of gastric cancer cells and its possible mechanism. Methods Gastric cancer MKN45 cells and AGS cells were cultured and divided into the control group(culture medium without DHAc)and treatment groups with different concentrations of DHAc(50,100,200,400,600,800,and 1 000 μmol/L).MTT assay and methylene blue(MB)assay were used to detect the effect of DHAc on the viability of MKN45 cells and AGS cells.The changes of mitochondrial membrane potential and the cell cycle distribution of MKN45 cells treated with DHAc were detected by flow cytometry,and its effects on the cell cycle of AGS cells were also analyzed.The effects of DHAc on the expression of proteins related to the cell cycle and autophagy in MKN45 cells were detected by Western blot. Results DHAc at different concentrations of 50,100,200,400,600,and 800 μmol/L showed significant inhibitory effects on proliferation of MKN45 cells.Among them,DHAc at the concentration range of 50-400 μmol/L also arrested the cell cycle of MKN45 cells at the G0/G1 phase,down-regulated the expressions of cyclin D1 and CDK4,and significantly reduced the mitochondrial membrane potential(P＜0.05);In the lower concentration range of 50-200 μmol/L,DHAc could induce autophagy in MKN45 cells,as manifested by the upregulation of the LC3-II/LC3-I ratio(P＜0.05).In addition,different concentrations of DHAc(100,200,400,600,800,and 1 000 μmol/L)could also significantly inhibit the proliferation of AGS cells.Among them,DHAc at the concentration range of 100-400 μmol/L could arrest the cell cycle of AGS cells at the G0/G1 phase(P＜0.05). Conclusion DHAc can inhibit the proliferation of gastric cancer cells.The possible mechanism is that DHAc arrests the cell cycle and induces autophagy in gastric cancer cells.

Key words: Dihydroactinidiolide, Gastric cancer cells, Cell proliferation, Cell cycle, Cell autophagy