JAK2/STAT3信号转导通路在岩大戟内酯B诱导的前列腺癌细胞PC-3凋亡中的作用

Effect of JAK2/STAT3 signaling transduction on the apoptosis of PC-3 cells of prostate cancer induced by Jolkinolide B

目的探讨岩大戟内酯B诱导的人前列腺癌细胞系PC-3细胞凋亡以及JAK2/STAT3信号转导通路在此过程中的作用。方法不同浓度的岩大戟内酯B处理人前列腺癌细胞系PC-3细胞0、24、48、72 h后,采用台盼蓝染色法检测PC-3细胞存活率;采用Annexin V-FITC/PI双染流式细胞仪检测PC-3细胞凋亡率;Western blot分析检测岩大戟内酯B作用不同时间后JAK2/STAT3信号转导通路的表达;预先用不同浓度的JSI-124(选择性STAT3途径抑制剂)处理PC-3细胞60 min,观察岩大戟内酯B作用不同时间后PC-3细胞的凋亡情况。结果岩大戟内酯B能够诱导前列腺癌细胞PC-3凋亡,降低磷酸化-JAK2/STAT3的表达,JSI-124可以提高岩大戟内酯B诱导的PC-3细胞凋亡率。结论 JAK2/STAT3信号转导通路参与了岩大戟内酯B诱导的PC-3细胞凋亡过程。JSI-124通过特异性地抑制STAT3活性提高了岩大戟内酯B诱导的PC-3细胞凋亡率。

Objective To investigate the role of the JAK2/STAT3 pathway in the apoptosis of prostate cancer PC-3 cells induced by Jolkinolide B, a bioactive diterpene isolated from the roots of Euphorbia fischeriana Steud. Methods The PC-3 cells were treated with different doses of Jolkinolide B at different time points. Growth inhibition was analyzed by trypan blue stain. Cell apoptosis of PC-3 cells was detected by Annexin V-FITC/PI staining. Expression of JAK2/STAT3 was detected by Western blot. In some experiments, PC-3 cells were pretreated with JSI-124 （an inhibitor for STAT3 ） , and the apoptosis rates of PC-3 cells were detected. Results We found that Jolkinolide B reduced cell viability and induced apoptosis in a dose- and time-dependent manner in PC-3 cells. The induction of apoptosis was accompanied by the down-regulation of phosphorylation-JAK2/STAT3. Moreover, we observed that JSI-124 treatment resulted in apoptosis of PC-3 cells. Conclusion The signaling pathway JAK2/STAT3 participates in the apoptosis of PC-3 cells induced by Jolkinolide B. JSI-124 increases PC-3 cell apoptosis induced by Jolkinolide B by inhibiting the activity of JAK2/STAT3.