The objective of the present study was to investigate whether ultrasound combined with microbubbles induces apoptotic cell death in androgen-independent prostate cancer cells and to identify the probable mechanism.We used ultrasound in continuous wave mode with a frequency of 21 kHz and a spatial-average temporal-average intensity of 46 mW/cm2.Ultrasound combined with microbubbles(200μL SonoVue)was used to treat androgen-independent human prostate cancer PC-3 cells for 30 s.PC-3 cells were divided into three groups:the control group,the ultrasound group and the ultrasound combined with microbubbles group.Immediately after treatment,trypan blue exclusion was used to assess cell viability.Cell apoptosis at 24 h after treatment was measured using transmission electron microscopy and flow cytometry.Western blotting was used to evaluate the expression of the apoptosis-related proteins,Bcl-2 and Bax.Ultrasound combined with microbubbles had a minimal effect on the viability of PC-3cells and induced minimal levels of cell lysis.The level of apoptosis in PC-3 cells induced by this modality was significantly higher than in controls(12.77±0.31%vs.2.56±0.22%,P<0.01).Treatment with ultrasound combined with microbubbles increased the expression of Bax,a pro-apoptotic protein,and decreased the expression of Bcl-2,an anti-apoptotic protein.It was concluded that ultrasound combined with microbubbles induces apoptotic cell death in human prostate cancer PC-3 cells through down-regulation of Bcl-2 and up-regulation of Bax.
BAI WenKunYANG ShaoLingSHEN EZHANG JiZhenSHEN ZhiYongHU Bing