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Anti-tumor efficacy of ultrasonic cavitation is potentiated by concurrent delivery of anti-angiogenic drug in colon cancer

Authors
  • Zhang, Chao
  • Huang, Pintong
  • Zhang, Ying
  • Chen, Jian
  • Shentu, Weihui
  • Sun, Yu
  • Yang, Zhijian
  • Chen, Shuyuan1, 2, 3, 4, 5, 6, 7
  • 1 Department of Ultrasonography
  • 2 The Second Affiliated Hospital of Zhejiang University College of Medicine
  • 3 Department of Surgery
  • 4 The Second Affiliated Hospital Zhejiang University College of Medicine
  • 5 Origin Biosciences Inc.
  • 6 Baylor Research Institute
  • 7 Baylor university medical center at Dallas
Type
Published Article
Journal
Cancer Letters
Publisher
Elsevier
Publication Date
Jan 01, 2014
Accepted Date
Jan 24, 2014
Volume
347
Issue
1
Pages
105–113
Identifiers
DOI: 10.1016/j.canlet.2014.01.022
Source
Elsevier
Keywords
License
Unknown

Abstract

This study investigated the efficacy of concurrent delivery of an anti-angiogenic drug and ultrasonic cavitation therapy in a mouse model of human colon cancer. A biotinylated form of the anti-angiogenic drug Endostar was conjugated to a streptavidin-coated microbubble (MB). Mice bearing subcutaneous tumors (HT29) were divided into 4 groups. Group 1 served as an untreated control. Group 2 served as a cavitation control and received naked microbubbles and sham ultrasonic cavitation (MB+sham cavitation). Group 3 received naked microbubbles and ultrasonic cavitation (MB+cavitation). Group 4 received Endostar loaded microbubbles and ultrasonic cavitation (Endostar-MB+cavitation). Ultrasonic cavitation was performed using a high-power custom built sonicator. Contrast-enhanced ultrasound imaging (CEUS) was used to measure tumor blood flow before and after ultrasonic cavitation. In vivo fluorescence imaging was performed to monitor changes in tumor volume. Immunohistochemistry was performed to assess CD31, VEGFR-2 and alpha-v beta-3 integrin expression within the tumor. Apoptosis of the tumor cells was determined by TUNEL assay, and ultrastructural changes within the tumor were examined by electron microcopy. Ultrasonic cavitation with Endostar-MB demonstrated a significantly greater inhibition of tumor blood flow on day 7 and tumor growth on day 16 compared with naked MB and control groups. The Endostar-MB treated mice showed significantly decreased expression VEGFR-2 and alpha-v beta-3 integrin, and increased apoptosis of tumor cells and degradation of the tumor ultrastructure. Our findings indicated that the anti-vascular and anti-tumor effects of ultrasonic cavitation could be potentiated by simultaneously delivering an anti-angiogenic drug in colon cancer.

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