An experimental research into endostatin microbubble combined with focused ultrasound for anti-tumor angiogenesis in colon cancer.
OBJECTIVE
to evaluate the therapeutic effect of targeted endostatin-loaded microbubbles, combined with improved, focused, directional ultrasound radiation for inhibition of subcutaneous translocation in situ colon tumor angiogenesis in colon cancer.


METHODS
65 BALB/c nude mice with subcutaneous translocation in situ colon tumors were randomly divided into five groups. Group A was the control group, without any treatments. In Group B, the mouse was treated with ultrasonic radiation. In Group C, the mouse was treated with ultrasonic radiation combined with empty SonoVue microbubbles. In Group D, the mouse was treated with ultrasonic radiation combined with empty Targestar-SA microbubbles. In Group E, the mouse was treated with ultrasonic radiation combined with endostatin microbubbles. The tumor size was measured before and 1, 14, and 28 days after irradiation. The peak intensity (PI), regional blood volume (RBV) and regional blood flow (RBF) were recorded using contrast-enhanced ultrasound. The tumor tissue was removed for pathological examination; the tumor necrosis area and microvascular density (MVD) were evaluated by immunohistochemistry.


RESULTS
Tumors in Groups C, D and E were significantly smaller than in Groups A and B at 28 days after irradiation, with Group E the smallest. PI, RBF and RBV of Groups C, D, and E were significantly decreased 28 days after radiation with Group E the lowest, and significantly lower than Groups A and B (all P < 0.05). The tumor tissue necrosis area of Group E was clearly greater while MVD was obviously lower than the other groups (all P < 0.01) at 28 days after treatment.


CONCLUSIONS
The targeted endostatin microbubbles, combined with focused, directional ultrasound radiation can damage tumor microvasculature of subcutaneous colon translocation in situ colon cancer, as well as inhibit the tumor angiogenesis.
Department of Colorectal Surgery, The Third People's Hospital of Hangzhou, Hangzhou City, Zhejiang, China Department of Ultrasonography, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou City, Zhejiang, China The Original Biological Science and Technology Co. Ltd., Nanjing City, Jiangsu, China Department of Ultrasonography, The Third People's Hospital of Hangzhou, Hangzhou City, Zhejiang, China.
Xiufeng
X
Zhang
Guangen
G
Yang
Ying
Y
Zhang
Pintong
P
Huang
Jianming
J
Qiu
Yu
Y
Sun
Zhong
Z
Shen
Xiujun
X
Liao
Hongsheng
H
Xia
Shuxian
S
Shao
Dong
D
Wang
colorectal cancer; endostatin; tumor angiogenesis; ultrasonic cavitation