Su Xiao-Ming, Jiang Tao, Zheng Lei, Peng Jin-Qiang, Sun Dong-Chen, Li Quan-Lin, Zhang Zhi-Wei
Department of Urology, The First Hospital Affiliated to Dalian Medical University, Dalian, Liaoning 116011, China.
Zhonghua Nan Ke Xue. 2013 Jul;19(7):583-7.
To explore the role of the P38 signaling pathway in the apoptosis of arsenic trioxide (As2 O3)-induced androgen-independent prostate cancer PC-3 cells.
Androgen-independent prostate cancer PC-3 cells were treated with different concentrations of As2 O3 for 24, 48 and 72 hours. The inhibitory effect of As2 O3 on the cell growth was measured by MTT, the expression 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.
As2 O3 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 biological activities. After 24 hours of treatment with As2 O3 at the concentrations of 2, 10 and 20 micromol/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 As2 O3 (P < 0.05).
As2 O3 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 P38 signaling pathway is involved in the apoptosis of As2 O3-induced androgen-independent prostate cancer PC-3 cells.
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。
用不同浓度的As2O3处理雄激素非依赖性前列腺癌PC-3细胞24、48和72小时。采用MTT法检测As2O3对细胞生长的抑制作用，用蛋白质免疫印迹法检测p-P38的表达，在使用高选择性P38抑制剂SB203580干扰P38信号通路前后，采用膜联蛋白V和碘化丙啶双染法测定细胞凋亡率。
As2O3以浓度和时间依赖性方式抑制PC-3细胞的增殖，并迅速激活P38磷酸化，从而充分发挥其生物学活性。用2、10和20μmol/L的As2O3处理24小时后，PC-3细胞的凋亡率分别为（18.9±0.43）%、（24.7±0.29）%和（49.7±1.79）%，在用SB203580干扰P38通路后，凋亡率分别降至（14.8±0.81）%、（22.1±0.51）%和（39.6±1.74）%。抑制P38通路可显著降低As2O3诱导的PC-3细胞凋亡（P<0.05）。
As2O3可通过激活P38信号通路诱导前列腺癌PC-3细胞凋亡，干扰P38信号通路可减少其凋亡，这表明P38信号通路参与了As2O3诱导的雄激素非依赖性前列腺癌PC-3细胞的凋亡。
