Wang Yu, Hu Bing, Diao Xuehong, Zhang Jizhen
Department of Ultrasound in Medicine, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
Exp Ther Med. 2012 Feb;3(2):187-191. doi: 10.3892/etm.2011.377. Epub 2011 Nov 7.
The aim of this study was to investigate the antitumor effect induced by low frequency (20 kHz) ultrasound (US) radiation combined with intravenous injection of microbubbles (Mbs) on prostate carcinoma Du145 xenografts in nude mice. Du145 prostate tumors were percutaneously implanted in 40 nude mice, which were randomly divided into 4 groups (n=10 each): US+Mbs, US, Mbs and control groups. The mice in the US+Mbs group were treated with 20 kHz, 200 mW/cm(2) US radiation and with 0.2 ml Mbs injected intravenously. Mice in the US and Mbs groups were only treated with US radiation and injection of Mbs, respectively. Tumors were measured with sonography, and the ratio of antitumor growth was calculated. The mice were sacrificed 14 days after treatment. Specimens of the tumor tissues were observed pathologically using light microscopy and transmission electron microscopy. Microvessel density and the average optical density of vascular endothelial growth factor were compared among groups by immunohistochemistry. The average gross tumor volume of the US+Mbs group was significantly reduced compared with the other groups following treatment (P<0.05). The ratio of the antitumor growth in the US+Mbs group was significantly greater than that of the US and Mbs group (P<0.05). Histological examination showed signs of tumor cell injury in the US+Mbs group. Examination by electron microscopy revealed vessel injury in the endothelium in the tumors treated with US+Mbs. Microvessel density and the average optical density of vascular endothelial growth factor in the US+Mbs group were significantly less than that of other groups (P<0.05). In conclusion, low frequency US of 20 kHz radiation combined with Mbs may be used to inhibit the growth of human prostate carcinoma xenografts in nude mice, and the effect is likely realized through microvessel destruction caused by cavitation.
本研究旨在探讨低频（20kHz）超声（US）辐射联合静脉注射微泡（Mbs）对裸鼠前列腺癌Du145异种移植瘤的抗肿瘤作用。将Du145前列腺肿瘤经皮植入40只裸鼠体内，随机分为4组（每组n = 10）：US+Mbs组、US组、Mbs组和对照组。US+Mbs组小鼠接受20kHz、200mW/cm²的US辐射，并静脉注射0.2ml Mbs。US组和Mbs组小鼠分别仅接受US辐射和注射Mbs。用超声检查测量肿瘤大小，并计算抗肿瘤生长率。治疗14天后处死小鼠。用光学显微镜和透射电子显微镜对肿瘤组织标本进行病理观察。通过免疫组织化学比较各组的微血管密度和血管内皮生长因子的平均光密度。治疗后，US+Mbs组的平均肿瘤总体积与其他组相比显著减小（P<0.05）。US+Mbs组的抗肿瘤生长率显著高于US组和Mbs组（P<0.05）。组织学检查显示US+Mbs组有肿瘤细胞损伤迹象。电子显微镜检查显示，US+Mbs治疗的肿瘤内皮有血管损伤。US+Mbs组的微血管密度和血管内皮生长因子的平均光密度显著低于其他组（P<0.05）。总之，20kHz的低频US辐射联合Mbs可用于抑制裸鼠体内人前列腺癌异种移植瘤的生长，其作用可能是通过空化引起的微血管破坏实现的。
