Effects of β-elemene on proliferation and apoptosis of cisplatin-resistant cells in human oral squamous cell carcinoma via PI3K/Akt pathway
Objective To investigate the effect of β-elemene(β-Ele)on the proliferation,apoptosis and drug resistance of cisplatinum(DDP)resistant human oral squamous cell carcinoma through PI3K/Akt pathway and its mechanism.Methods The cisplatin-resistant cell line CAL-27/DDP was constructed.The cells were divided into control group,β-Ele group(40 μg/ml β-Ele),DDP group(2 mg/L DDP),β-Ele+DDP group(40 μg/ml β-Ele combined with 2 mg/L DDP)and β-Ele+DDP+740Y-P group(40μg/ml β-Ele,2 mg/L DDP and 50 μg/ml 740Y-P).MTT assay was used to detect the proliferation activity of the cells,and the half maximal inhibitory concentration(IC50)was calculated.Flow cytometry to detect cell cycle and apoptosis.Western blotting was used to detect the expression of PI3K/Akt pathway-related proteins.Results IC50 of CAL-27/DDP cells to DPP was 5.53 mg/L,which was significantly higher than that of CAL-27 cells to DPP(1.45 mg/L).Compared with the control group,the proliferation activity of CAL-27/DDP cells was decreased,the apoptosis rate was increased,and the relative expression of p-PI3K and p-Akt were decreased in β-Ele group and DDP group after 72 h.The cells in β-Ele group were arrested at S phase,while the cells in DDP group were arrested at G0/G1 phase(P<0.05).Compared with the DDP group,the cell proliferation activity of the β-Ele+DDP group was further decreased,the cell cycle was arrested at G0/G1 phase,the apoptosis rate was increased,the relative expression of p-PI3K and p-Akt were decreased(P<0.05).Compared with β-Ele+DDP group,the expression of p-PI3K and p-Akt protein,the proliferation activity of CAL-27/DDP cells were increased in β-Ele+DDP+740Y-P group,while the percentage of apoptosis was decreased(P<0.05).Conclusion β-Ele inhibits the proliferation and promotes apoptosis of CAL-27/DDP cells by inhibiting the activation of the PI3K/Akt signaling pathway,thereby reducing the resistance of CAL-27/DDP cells to DDP.