Inhibitory effects of subcutaneous tumors in nude mice mediated by low-frequency ultrasound and microbubbles.
The aim of the present study was to investigate the sonication effects of 21-kHz ultrasound (US) with microbubbles (MBs) on the subcutaneous prostate tumors of nude mice. In total, 15 tumor-bearing nude mice were divided into three groups: The control group, the low-frequency US group and the US+MB group. The MBs used were from US contrast agent SonoVue. The parameters of the US were as follows: 21 kHz, 26 mW/cm2and a 40% duty cycle (2 sec on, 3 sec off) for 3 min, once every other day for 2 weeks. Color Doppler flow imaging, hematoxylin and eosin (HE) staining, immunoblotting and transmission electron microscopy (TEM) were used to evaluate the results. Following 2 weeks of treatment, the blood flow signal disappeared in the US+MB group only, and the tumor size was smaller when compared with the control and US groups. For the immunoblotting, the intensity of cyclooxygenase-2 and vascular endothelial growth factor in the US+MB group was lower compared with the other two groups. Tumor necrosis was present and the nucleus disappeared upon HE staining in the US+MB group. Upon TEM analysis, increased cytoplasmic vacuolation and dilatation of the perinuclear cisternae of the tumor cells were found in the US+MB group. In the control and US groups, the tumors had intact vascular endothelia and vessel lumens. However, lumen occlusion of the vessels was observed in the US+MB group. In conclusion, 21-kHz low-intensity US with MBs may result in vessel occlusion and growth inhibitory effects in the subcutaneous tumors of nude mice.
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China ; Department of Radiology, Nantong Tumor Hospital Affiliated to Nantong University, Nantong, Jiangsu 226361, P.R. China.
Zhi-Yong
ZY
Shen
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
E
E
Shen
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
Xue-Hong
XH
Diao
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
Wen-Kun
WK
Bai
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
Min-Xia
MX
Zeng
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
Yan Yan
YY
Luan
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
Shu-Liang
SL
Nan
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
Yan-Duan
YD
Lin
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
Cong
C
Wei
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
Li
L
Chen
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
DI
D
Sun
Department of Ultrasound in Medicine, Shanghai Institute of Ultrasound in Medicine, Sixth People's Hospital Affiliated to Shanghai Jiaotong University, Shanghai Jiaotong University School of Medicine, Shanghai 200233, P.R. China.
Bing
B
Hu
cavitation; low frequency; microbubbles; ultrasound