Abstract:
Objective: To investigate the effects of perifosine,an Akt inhibitor,combined with cisplatin on the proliferation and apoptosis of gastric cancer cell line BGC-823.
Methods: The gastric cancer cell line BGC-823 was cultured
in vitro,the cells were stimulated with cisplatin and collected at 0,12,24,36 h of stimulation,and the phosphorylation level of Akt in BGC-823 cells was detected at different time points.The blank group was treated without any treatment,both the cisplatin group and combination group were treated with cisplatin,and the combination group were additionally treated with perifosine at the same time.The cell proliferation,migration,apoptosis,DNA damage,expression levels of MMP-2,MMP-9 and N-cadherin,activation of apoptotic proteins PARP1 and caspase 1 and phosphorylation levels of Akt were detected.
Results: The phosphorylation level of Akt in BGC-823 cells was significantly increased with the prolongation of stimulation time(
P<0.05).Compared with the blank group,cisplatin stimulation inhibited the cell proliferation,and promoted cell apoptosis significantly(
P<0.01).Compared with the cisplatin group,the cell proliferation rate decreased(
P<0.01),the cell migration ability decreased(
P<0.01),and the degree of apoptosis and DNA damage increased in the combination group(
P<0.05).The expression levels of MMP-2,MMP-9 and N-cadherin and contents of PARP1 and caspase 1 decreased(
P<0.01),and the phosphorylation level of Akt decreased in the combination group compared with the cisplatin group(
P<0.01).
Conclusions: Perifosine can enhance the sensitivity of cisplatin to gastric cancer cells by inhibiting the phosphorylation of Akt,and inhibit the proliferation and promote the apoptosis of gastric cancer cells.