Validation of Bevacizumab Therapy Effect on Colon Cancer Subtypes by Using Whole Body Imaging in Mice.

Abstract

Preclinical imaging offers a useful tool for monitoring cancer biological behavior and therapy in vivo without the necessity of animal surgery. The following paper describes our examination of tumor progress and anti-angiogenic therapy with Bevacizumab on colon cancer subtypes (SW480 and SW620) by using different non-invasive real-time in vivo imaging techniques. Color Doppler ultrasound imaging (CDUI) was used to observe the formation of new blood vessels; a homemade fluorescence reflectance imaging (FRI) apparatus was mainly used to test the difference in VEGFR2 expression between the tumor subtypes. Briefly, 15 Balb/c nude mice bearing subcutaneous SW480 and SW620 xenografts were randomly divided into Control and Drug groups. Bevacizumab treatment lasted for 3weeks. All images were captured pre- and post-treatment. At the end of experiment, all mice were euthanized, and tumor tissue was collected and analyzed by immunohistochemical staining. Expression of VEGFR2 was found to be slightly (10%) but significantly higher for the SW620 cells than for SW480 cells. In addition, SW620 has shown to be more vascularized than SW480 subtype. After 3-week Bevacizumab therapy, no blood vessels were found within 83% of SW620, while it was 67% in SW480; the increase of SW620 tumor volume post-treatment was only 3.17-fold compared with the tumor volume pre-treatment, and 4.51-fold higher in SW480. Our data suggest that SW480 and SW620 cell lines respond differently to Bevacizumab therapy in vivo. Because of higher vascularization, and subsequently higher reduction by drug of new blood vessels and tumor growth rate, xenografts derived from the metastatic SW620 cell line have a better chance of being successfully treated with Bevacizumab compared with those derived from the primary tumor SW480 cell line.