青蒿琥酯诱导人前列腺癌PC-3细胞分化及周期阻滞

Artesunate induces prostate cancer cell line PC-3 differentiation and cell cycle arrest

目的:探讨青蒿琥酯(artesunate,ART)对人前列腺癌细胞株PC-3分化及周期阻滞的影响。方法:培养人前列腺癌PC-3细胞至对数生长期,ART处理PC-3细胞48h后,流式细胞术(flow cytometry,FCM)检测PC-3细胞的细胞周期分布状况,酶联免疫吸附测定法检测细胞培养上清液前列腺特异性抗原(prostate specific antigen,PSA)含量,透射电镜观察细胞形态学变化。结果:与空白对照组比较,ART高剂量组PC-3细胞G0/G1+S期比率减少明显(P<0.05)。ART高剂量组和中剂量组PC-3细胞G2/M比例高于顺铂组和空白对照组(P<0.05);ART各剂量组细胞上清液中PSA水平均低于空白对照组,差异有统计学意义(P<0.05,P<0.01)。透射电镜观察显示细胞胞浆内出现空泡,细胞极性增强,细胞核靠向细胞一侧,对侧的微绒毛明显增多。结论:青蒿琥酯有诱导人前列腺癌PC-3细胞周期阻滞的作用,并能一定程度地诱导前列腺癌PC-3细胞分化。

Objective： To explore the effect of artesunate （ART） on cell differentiation and cell cycle distribution of the prostate cancer cell line PC-3 in vitro. Methods： PC-3 cells were cultivated with ART from logarithmic growth phase. After 48-hour treatment, the cell cycles were detected by flow cytometry （FCM）, and enzyme linked immunosorbent assay was used to detect the level of prostate specific antigen （PSA） in cell culture supernatant. The change of cellular morphology was observed under a transmission electron microscope （TEM）. Results： In comparison with the blank control group, the rate of G0/G1 plus S stages of PC-3 cells was significantly decreased in the high-dose ART group. The PC-3 cell was arrested in G2/M by ART. The rates of G2/M of the high-dose ART group and the medium-dose ART group were obviously higher than those of the blank control group and the cisplatin group （P〈0.05）. The levels of PSA in the three ART groups were significantly lower than that of the normal control group （P〈0.05, P〈0.01）. In the ART groups, TEM showed that some vacuoles appeared in endochylema, cell polarity was enhanced, cell nucleus leaned to one side of the cell, and microvilli increased on the other side of the cell. Conclusion： ART can induce PC-3 cell cycle arrest and differentiation in vitro.