Mechanism of radiosensitization effect of paeonol on human lung adenocarcinoma cell line A549

Objective To investigate the radiosensitization effect and underlying mechanism of Paeonol on human lung adenocarcinoma cell line A549 in vitro. Methods Cells were assigned to following groups:control,Paeonol alone,irradiation alone,Paeonol combined with irradiation.The effect of Paeonol on cell proliferation was evaluated by the MTT assay. Clonogenic assay was performed to measure the radiosensitization effect of Paeonol under three concentrations around 20％ IC50.Cell apoptosis was determined by TUNEL assay and flow cytometry (FCM).The expression of Survivin protein was analyzed by Western blot.Results Cell growth was inhibited by Paeonol in a dose-dependent manner and the IC50 of Paeonol was (25.2 ± 2.1 ) mg/L. Clonogenic assay showed that Paeonol could markedly enhance cell radiosensitivity and the sensitizing enhancement ratio (SER) was 1.29.After the pretreatment of Paeonol with different concentrations,radiation-induced apoptosis increased with the doses at 24,48,and 72 h post-irradiation ( t =4.95,3.03,3.78,4.59,2.88,3.70,5.54,P ＜ 0.05 ). Moreover,the protein expression of Survivin was obviously down-regulated by 22.6％ - 56.7％ ( t =4.15,7.30,13.47,P ＜0.05 ) due to the treatment of Paeonol.When the Paeonol-treated cells were further irradiated with 6 Gy X-rays,the expression of Survivin was reduced to 22.2％ - 69.4％ ( t =4.30,8.36,16.34,P ＜ 0.05 ).Conclusions Paeonol had radiosensitization effect on the human lung adenocarcinoma cell line A549 in vitro,where the down-regulated Survivin protein might be involved. Key words: Radiosensitization ;  Paeonol ;  Apoptosis;  A549 ;  Survivin protein