Effect and mechanism of atorvastatin on the proliferation，autophagy and glucose metabolism of AGS cells in human gastric cancer / 中国药房

ABSTRACT

OBJECTIVE To explore the effects and mechanism of atorvastatin on the proliferation， autophagy and glucose metabolism of AGS cells in human gastric cancer. METHODS The effects of low， medium and high concentrations of atorvastatin （12.5， 25， 50 μmol/L） on the viability of AGS cells were investigated through preliminary experiments， and the concentration of action was screened. The formal experiment was divided into control group （no intervention）， atorvastatin group （25 μmol/L）， positive control group （50 mg/L 5-fluorouracil）， inhibitor group [25 μmol/L atorvastatin +10 μmol/L phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt） signaling pathway inhibitor LY294002] and activator group （25 μmol/L atorvastatin +10 μmol/L PI3K/Akt signaling pathway activator SC79）， all of which were treated for 24 h. Glucose metabolism （glucose and lactic acid contents） and cell proliferation rate were detected， as well as the expression of autophagy-associated protein light chain 3 （LC3） Ⅰ， LC3Ⅱ and PI3K/Akt signaling pathway-associated proteins in cells. RESULTS Both medium and high concentrations of atorvastatin could significantly inhibit the viability of AGS cells （P＜0.05）， and 25 μmol/L atorvastatin was selected for the official experiment for follow-up experiments. Compared with the control group， the contents of glucose and lactic acid， cell proliferation rate， p-PI3K/PI3K and p-Akt/Akt ratios in the positive control group and atorvastatin group were significantly decreased （P＜ 0.05）， and the protein expression levels of LC3 Ⅰ and LC3 Ⅱ were significantly increased （P＜0.05）. Compared with the atorvastatin group， the inhibitor further promoted the changes in the above indexes （P＜0.05）， and the activator significantly reversed the changes in the above indexes （P＜0.05）. CONCLUSIONS Atorvastatin could inhibit glucose metabolism and proliferation of AGS cells in human gastric cancer and promote autophagy. The mechanism may be related to the inhibition of the PI3K/Akt signaling pathway.