摘要
目的:探讨P38信号通路在三氧化二砷(As2O3)诱导雄激素非依赖性前列腺癌PC-3细胞凋亡中的作用。方法:应用四甲基偶氮唑蓝(MTT)法检测不同浓度(0.312 5、0.625、1.25、2.5、5、10、20μmol/L)As2O3作用PC-3细胞24、48、72 h后的细胞生长抑制情况。Western印迹检测As2O3作用PC-3细胞后P38信号转导通路的表达。Annexin V/PI双染色法检测As2O3作用PC-3细胞后细胞凋亡,同时检测应用P38通路高选择抑制剂SB203580干扰P38信号通路后As2O3诱导PC-3细胞凋亡的变化。结果:As2O3诱导PC-3细胞凋亡呈现时间、剂量依赖性。As2O3可以使P38信号通路蛋白快速磷酸化,激活P38信号通路。2、10、20μmol/L As2O3作用PC-3细胞24 h后,PC-3细胞凋亡率分别为(18.9±0.43)%、(24.7±0.29)%和(49.7±1.79)%。应用P38信号通路高选择抑制剂SB203580干扰P38信号通路后,PC-3细胞凋亡率分别降低为(14.8±0.81)%、(22.1±0.51)%和(39.6±1.74)%,抑制P38信号通路可以显著降低As2O3诱导PC-3细胞的凋亡(P<0.05)。结论:P38信号通路在As2O3诱导雄激素非依赖性前列腺癌PC-3细胞凋亡中有表达,干扰P38信号通路可影响As2O3诱导PC-3细胞凋亡,提示P38信号通路参与了As2O3诱导的PC-3细胞凋亡。
Objective: To explore the role of the P38 signaling pathway in the apoptosis of arsenic trioxide ( As2O3 ) -induced an- drogen-independent prostate cancer PC-3 cells. Methods: Androgen-independent prostate cancer PC-3 cells were treated with differ- ent concentrations of As2O3 for 24, 48 and 72 hours. The inhibitory effect of As2O3 on the cell growth was measured by MTT, the ex- pression of p- P38 detected by Western blot, and the rate of cell apoptosis determined by Annexin V and PI double staining before and after interfering the P38 signaling pathway by SB203580, a highly selective P38 inhibitor. Results: As2O3 inhibited the proliferation of PC-3 cells in a concentration- and time-dependent manner, and quickly activated P38 phosphorylation, thus giving full play to its biolog- ical activities. After 24 hours of treatment with As2O3 at the concentrations of 2, 10 and 20 μmol/L, the apoptosis rates of the PC-3 cells were ( 18.9 ± 0.43 ), (24.7 ± 0.29) and ( 49.7 ± 1.79 ) %, respectively, which were reduced to ( 14.8 ± 0.81 ), ( 22. 1 ± 0.51 ) and (39.6 ± 1.74)% after interfering the P38 pathway with SB203580. Inhibition of the P38 pathway significantly reduced the apoptosis of the PC-3 cells induced by As2O3 ( P 〈 0.05 ). Conclusion : As2O3 can induce the apoptosis of prostate cancer PC-3 cells by activating the P38 signaling pathway, and interfering the P38 signaling pathway can reduce their apoptosis, which suggests that the P38signaling pathway is involved in the apoptosis of As2O3-induced androgen-independent prostate cancer PC-3 cells.
出处
《中华男科学杂志》
CAS
CSCD
2013年第7期583-587,共5页
National Journal of Andrology
基金
国家自然科学基金(21272032)~~