Role of P21 protein and XIAP on apoptosis-inducing effect by mevastatin against A549 cell line / 基础医学与临床

ABSTRACT

Objective To investigate the role of P21 protein and XIAP on apoptosis-inducing effect by mevastatin against A549 cell line and its mechanisms. Methods The cells proliferation was detected by MTT assay. The cell cycle distribution and apoptosis induction were evaluated with flow cytometer and electron microscopy. The mRNA expression of P21 and XIAP was measured with reverse transcription-polymerase chain reaction.The protein expression of P21 and XIAP was tested with flow cytometer and Western Bolt respectively. Results Mevastatin inhibited A549 cell survival in a time-dependent and concentration-depended manner. Flow cytometry showed that mevastatin induced G0/G1 phase arrest and caused apoptosis. Mevastatin did not affect P21 expression at both mRNA and total protein level.Concomitantly,P21 protein localized on cellular membrane decreased.Both mRNA and protein expression in XIAP were down regulated by mevastatin. All these effects were reversed by mevalonate.Conclusion Mevastatin can inhibite proliferation,induce apoptosis and interfere with cell progression of A549 through mevalonate pathway. Its mechanisms are explained by decreasing the expression of XIAP mRNA and protern.Targeting HMG-CoA reductase,Mevastatin blocks the isoprenylation of P21 protein which affects its anchorage on the cellular membrane.