Effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji cells and its mechanism / 中华血液学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the effect of ERK1/2 inhibitor AZD8330 on human Burkitt's lymphoma cell line Raji cells and its mechanism.</p><p><b>METHODS</b>Raji cells were treated with different concentrations of AZD8330. CCK-8 was used to detect the cell viability. The apoptosis rate of Raji cells was detected by flow cytometry using Annexin V/PI-staining. Real-time PCR was used to assess the expression of Bcl-2, Bcl-xl, caspase-3 and VEGF genes. The protein expression level of Bcl-2, Bcl-xl, caspase-3 and p-ERK1/2 was tested with Western blot.</p><p><b>RESULTS</b>The cell survival rate decreased to(62.09±0.86)%,(50.06±1.33)% and (39.13±2.34)% respectively after cells were treated with AZD8330 at 1.00 μmol/L in vitro for 24 h, 48 h and 72 h, and statistically significant differences were observed in groups with different time of treatment(P<0.05). Apoptosis of cells treated with AZD8330 at 0.10, 1.00, 10.00 μmol/L in vitro for 24 h, 48 h and 72 h was analyzed, and the statistically significant differences were observed in groups of different time and concentration treatment (P<0.05). AZD8330 induced Raji cell apoptosis and upregulated expression of Bcl-2, Bcl-xl, VEFG and decreased the expression of caspase-3 in a dose and time dependent manner, and statistically significant differences were observed in groups of different time and concentration treatment (P<0.05). At the same time, the Bcl-2, Bcl-xl and p-ERK1/2 proteins expression is suppressed obviously, but the expression of caspase-3 protein increased.</p><p><b>CONCLUSION</b>AZD8330 induces cell apoptosis by down-regulating the activation of ERK1/2 signal transduction pathway in Burkitt's lymphoma cell line Raji cells in a dose and time dependent manner.</p>