阿法替尼对前列腺癌细胞增殖和凋亡的影响

Effect of afatinib on proliferation and apoptosis of prostate cancer cells

目的观察阿法替尼对前列腺癌C4-2细胞增殖和凋亡的影响。方法实验组C4-2细胞给予1.0μg·mL^(-1)阿法替尼处理,对照组给予等量0.9%NaCl,抑制剂组给予100 ng·mL^(-1)AG490。用噻唑蓝(MTT)法检测C4-2细胞的增殖抑制率,用流式细胞术检测细胞的凋亡率,用蛋白质印迹(Western blot)法检测细胞中Janus激酶2(Janus kinase 2,JAK2)、信号转导因子和转录活化因子3(signal transducer and activator of transcription 3,STAT3)、磷酸化JAK2(p-JAK2)、磷酸化-STAT3(p-STAT3)的蛋白表达。结果对照组、实验组的凋亡率分别为(6.98±0.53)%,(24.82±0.19)%,差异有统计学意义(P<0.05)。给药24 h后,对照组、抑制剂组的增殖抑制率分别为0,(30.79±2.66)%,凋亡率分别为(8.16±0.49)%,(23.78±1.93)%,差异有统计学意义(P<0.05)。对照组、实验组的JAK2表达量分别为0.97±0.03,0.64±0.05,STAT3蛋白表达量分别为1.04±0.11,0.70±0.06,p-JAK2蛋白表达量分别为0.59±0.05,0.38±0.03,p-STAT3蛋白表达量分别为0.52±0.04,0.24±0.02,差异均有统计学意义(均P<0.05)。结论阿法替尼可抑制前列腺癌细胞的增殖并促进凋亡,其机制可能与JAK2/STAT3信号通路的抑制相关。

Objective To observe the effect of afatinib on proliferation and apoptosis of prostate cancer C4-2 cells. Methods The C4-2 cells in test group were treated with 1.0 μg·mL;afatinib, the cells in control group were treated with 0.9% NaCl, the cells in inhibitor group were treated with 100 ng·mL;AG490. The proliferation inhibition rate of C4-2 cells was determined by thiazolam(MTT), cell apoptosis rate was detected by flow cytometry, the expressions of Janus kinase 2(JAK2), signal transducer and activator of transcription 3(STAT3), phosphorylated-JAK2(p-JAK2) and phosphorylated-STAT3(p-STAT3) protein in cells were detected by Western blot. Results The apoptosis rates of control group, test group were(6.98±0.53)%,(24.82±0.19)%, the difference was statistically significant(P<0.05). At 24 h after treatment, the proliferation inhibiting rates of control group, inhibitor group were 0,(30.79±2.66)%, the apoptosis rates were(8.16±0.49)%,(23.78±1.93)%, the differences were statistically significant(P<0.05). The expression of JAK2 in control group and test group were 0.97±0.03 and 0.64±0.05,the expression of STAT3 protein were 1. 04 ± 0. 11 and 0. 70 ± 0. 06,the expression of p-JAK2 protein were0. 59 ± 0. 05 and 0. 38 ± 0. 03,the expression of p-STAT3 protein were 0. 52 ± 0. 04 and 0. 24 ± 0. 02,the differences were all statistically significant( all P < 0. 05). Conclusion Afatinib can inhibit the proliferation of prostate cancer cells and promote apoptosis. The mechanism may be related to the inhibition of JAK2/STAT3 signaling pathway.