A novel therapeutic strategy using ultrasound mediated microbubbles destruction to treat colon cancer in a mouse model

The goal of this study was to determine whether ultrasound mediated microbubbles destruction (UMMD) could inhibit colon cancer growth in a mouse model. Six-week-old balb/c female nude mice were subcutaneously inoculated with HT29-GFP cells (HT29 cells labeled with green fluorescent dye) in axilla to establish a xenograft mouse model of colon carcinoma, which were randomly divided into five groups (n = 10 each): group A (blank group): no treatment; group B (saline only); group C (saline + ultrasound exposure); group D (intravenous microbubbles only); and group E (intravenous microbubbles + ultrasound exposure). Treatment of each group was performed on days 20, 21, and 22 after inoculation. Tumor growth and metastatic spread were monitored by the whole-body fluorescent imaging, tumor volume growth and body weight growth curve were obtained as well. The mice were euthanized 30 days after treatment. Specimens of the tumor tissues were evaluated pathologically using light microscopy and transmission electron microscopy. Necrosis percentages, microvascular density and tumor cells damage of each tumor were assessed histologically. Our data indicate that: (1) tumor growth in group E (intravenous microbubbles + ultrasound exposure) was significantly decreased after four weeks post inoculation, compared with other control treatments (P < 0.05); (2) the tumor weight at sacrifice in group E was significantly lower than that in other groups; (3) The intravenous microbubbles combined with ultrasound exposure treated mice showed significantly decreased expression levels of CD31. (4)The pathological changes of absence of nucleus membrane, chromatin condensation, mitochondrial vacuolation and hemorrhagic damage of microvessel were observed in the tumors of group E only, whereas these changes occurred rarely in other groups; and (5) no metastatic lesion was found in any group throughout this study using whole-body fluorescent imaging, and the skin of the mouse in group E was intact after UMMD treatment. Our results suggest that UMMD can be used as a promising novel therapeutic strategy to treat colon cancer.

► UMMD not only can disrupt the tumor microvessels, but also produce tumor cell injury and lysis.
► UMMD was a safe and feasible technique to facilitate the tumor therapy, which could improve animal survival status.
► UMMD can be potentially translated into clinical practice in the future.