内皮素A受体拮抗剂BQ123对前列腺癌PC-3M细胞增殖与凋亡的影响

目的:观察内皮素A受体拮抗剂BQ123对转移性前列腺癌(PCa)PC-3M细胞株增殖与凋亡的影响,初步探讨内皮素A受体拮抗剂对转移性PCa细胞的体外抗肿瘤效应。方法:实验分为两组,对照组为PC-3M细胞及含灭活小牛血清的F12/RMPI1640培养液;实验组为PC-3M细胞加入等量的1μmol/LBQ123。采用四甲基偶氮唑蓝(MTT)比色法、划痕损伤实验、细胞迁移实验观察BQ123对人PCaPC-3M细胞株增殖的抑制效应,利用Annexin V-FITC/PI染色和流式细胞术检测BQ123诱导PC-3M细胞凋亡的作用及其与细胞周期的关系。结果:MTT比色法结果显示BQ123随着作用时间的增加,对PC-3M的抑制率分别为24h22.32%、48h44.88%和72h64.47%,表现出良好的时效关系(P<0.05),划痕损伤实验结果提示:实验组PC-3M细胞的迁移距离分别为12h(103.42±75.63)μm、24h(243.75±121.53)μm和48h(422.07±36.01)μm,均低于对照组的12h(162.93±19.87)μm、24h(317.19±43.19)μm和48h(692.74±40.84)μm(P<0.05)。细胞迁移实验中实验组穿入下室的PC-3M细胞为(79.2±9.58)个,亦明显少于对照组的(92.6±5.94)个(P<0.05);Annexin V-FITC/PI双染色法的结果显示对照组PC-3M细胞凋亡率为(9.38±1.37)%,实验组PC-3M细胞凋亡率为(15.03±0.93)%,差异有统计学意义(P<0.05),细胞周期实验的结果显示实验组各期细胞比例与对照组相比差异不显著(P>0.05)。结论:BQ123对PCaPC-3M细胞株的生长、迁移和侵袭能力均有明显的抑制作用,且可以诱导PC-3M细胞凋亡,可为PCa治疗的研究提供一种新的思路。

Effects of Endothelin A Receptor Antagonist BQ123 on the Proliferation and Apoptosis of Prostate Cancer Cell Line PC-3M

Objective： To investigate the anti-tumor effect of the endothelin A receptor antagonist BQ123 on human prostate cancer cell line PC-3M in vitro by observing its impact on the proliferation and apoptosis of human prostate cancer cells. Methods ： The inhibiting effect of BQ123 on the proliferation of PC-3M cells was observed by MTT assay, erasion trace test and Traswell chamber chemotaxis assay, and its induction of their apoptosis determined by Annexin V-FITC/PI staining and cytometry. Results： BQ123 exhibited increased inhibition of PC-3M cells in a time-dependant manner, with inhibition rates of 22.32%, 44.88% and 64.47% at 24 h, 48 h and 72 h, respectively （P 〈 0.05）. The migration distances of the PC-3M cells in the BQ123 group were （103.42±75.63 ） μm, （243.75±121.53） μm and （422.07±36. 01 ） μm at 12 h, 24 h and 48 h, obviously lower than （ 162.93±19.87 ） μm, （317.19±43.19） μm and （692.74±40.84） μm in the control group （P 〈 0. 05）. The number of the PC-3M cells that invaded the inferior chamber in the BQ123 group was （79.2 ± 9.58 ）, significantly decreased as compared with （92.6 ± 5.94） in the control （ P 〈 0. 05 ）. The apoptosis rate of PC-3M exposed to BQ123 was （ 15.03 ± 0.93 ） %, significantly higher than （9.38 ±1.37） % in the control （P 〈 0.05 ）. The ratio of PC-3M cells in different cycles showed no significant differences. Conclusion ： BQ123 inhibits the proliferation of PC-3M cells and induces their apoptosis in vitro, which may give a new idea on the studies of prostate eancer therapies.