Abstract:

Objective To explore the influences of withaferin A （WFA） on proliferation， apoptosis and PI3K／Akt signaling pathway of non-small cell lung cancer （NSCLC） A549 cell. Methods The A549 cells were treated with different concentrations of WFA （0， 2.5， 5.0， 10.0， 20.0 μmol／L）. The MTT assay was used to measure the proliferation inhibition rates at 24， 48， 72 and 96h treated with different concentrations of WFA. The Hoechst staining and Annexin V-FITC／PI double staining were employed to detect cell apoptosis after treatment with different concentrations of WFA. The cycle distribution at 48h after treatment with WFA was detected by flow cytometry. The Western blotting was used to measure the protein levels of apoptosisrelated genes （Bcl-2， Bax and Cleaved caspase-3）， Akt and its phosphorylated form （P-Akt）. Results WFA could increase the proliferation inhibition rates in a dose- and time-dependent manner（P＜0.05）. The apoptotic indices of A549 cells after treatment with different concentrations of WFA （0， 2.5， 5.0， 10.0， 20.0 μmol／L） were 2.75±0.64， 4.6±1.36， 9.75±2.78， 12.92±3.42 and 18.68±4.31 with significant differences （P＜0.05）. In addition to 2.5μmol／L group， the early and late apoptosis rates， protein levels of apoptosis-promoting genes （Bax and Cleaved caspase-3） and the cell proportion in G0／G1phase of the remaining concentration groups were higher than those of 0μmo／L group（P＜0.05）.The p-Akt／Akt value decreased with increasing concentration and the differences were statistically significant among concentrations （P＜0.05）. Conclusion WFA can inhibit the proliferation and apoptosis of A549 cell possibly by inhibiting the activation of PI3K／Akt pathway activation.