Propofol Reduces Apoptosis Through PI3K/Akt Pathway in Alveolar Epithelial Cells

Objectives: Propofol is an intravenous anesthetic agent widely used to introduce and maintain anesthesia during oral surgical procedures. It has drawn greater attention due to its anti-inflammatory effect and anti-apoptosis capability. We have previously reported that propofol has potential to reduce apoptosis through down-regulation of SAPK/JNK, c-Jun, and Bim in AECs. The present investigation was undertaken to clarify the effect and mechanism of propofol on apoptosis in respect to PI3K/Akt signaling pathway in AECs.
Methods: AECs, A549 cells, were purchased from DS Pharma Biomedical Co., Ltd. AECs were cultured to semi-confluence and treated with 25μM propofol and/or 1μM hydrogen peroxide (H₂O₂) for 1 or 12 hours at 37°C. The percentage of apoptotic cells was measured by flow cytometry analysis. The number of apoptotic cells and the cell cycle phase distribution in AECs were quantified using the CycleTEST™ PLUS DNA reagent kit and the FACS Calibur. The phosphorylation and expression of Akt，GSK-3β，PTEN，PDK1，P21^Waf1/Cip1，and P27 ^Kip1 were measured by western blot analysis.
Results: H₂O₂ at 1μM significantly increased the percentage of Sub-G₁ phase cells compared to the control (P<0.001). Propofol at 25μM significantly reduced the percentage of Sub-G₁ phase cells at 12 hours in H₂O₂-treated AECs (P<0.001). Propofol at 25μM significantly decreased Akt (Ser473) phosphorylation and P21^Waf1/Cip1 expression compared to the control (P<0.05), and also it significantly increased GSK-3β (Ser9) phosphorylation compared to the control (P<0.05).
Conclusions: Propofol decreased P21^Waf1/Cip1, cyclin-dependent kinase inhibitor, expression through decreasing Akt phosphorylation and increasing GSK-3β phosphorylation. These results suggest that propofol reduces apoptosis by affecting cell cycle through the Akt/GSK-3β/P21^Waf1/Cip1 pathway in AECs.