Abstract:
Objective To investigate the effect of ADRB2 silencing on the cisplatin-resistance and the cell proliferation and apoptosis of epithelial ovarian cancer cells.
Methods Human epithelial ovarian cancer cell line SKOV3/DDP was selected for the study and small RNA interference technology was used for silencing the expression of ADRB2. The experiment was divided into 4 groups:ADRB2 shRNA1 group, ADRB2 shRNA2 group, negative control group and blank control group. Cells were treated with different concentration of cisplatin (0, 2.5, 5, 10, 20, 40 μmol/L). Cell proliferation was measured by CCK-8 assay, cell apoptosis was measured by flow cytometry, the expression of caspase-9, Bcl-2 and Bax were measured by western blot. Data was analyzed by
t test.
Results Cell growth inhibitory rate was significantly upregulated in a dose depend manner upon cisplatin treatment in four groups. The IC50 of two ADRB2 shRNA group were (29±8)μmol/L and (32±11)μmol/L, significantly lower than those of negative control group[(104±15)μmol/L,
P<0.01] and blank control group[(112±10)μmol/L,
P<0.01]. Cell apoptosis rate was upregulated in an dose depend manner upon cisplatin treatment in four groups. Cell apoptosis of two ADRB2 shRNA group were significantly higher than those of negative control group and blank control group (
P<0.01). The caspase-9 and Bax expression were increased upon cisplatin treatment. The levels in two ADRB2 shRNA group were significantly higher than those of negative control group and blank control group (
P<0.05). The Bcl-2 expression was decreased upon cisplatin treatment. Its level in two ADRB2 shRNA group were significantly lower than those of negative control group and blank control group (
P<0.05).
Conclusion ADRB2 silencing significantly increase cisplatin-induced apoptosis and reduce the cell proliferation induced by cisplatin in SKOV3/DDP cells through regulating caspase and Bcl-2 apoptosis signaling pathway.