Inhibition of Walker-256 Tumor Growth by Combining Microbubble-Enhanced Ultrasound and Endostar

Objectives This research is to investigate the anti-tumor effects by combining anti-vascular effect of microbubble enhanced ultrasound (MEUS) mechanical destruction and anti-angiogenic effect of Endostar. Methods Rats bearing Walker-256 tumor were randomly divided into 4 groups treated by Endostar + MEUS combination, Endostar, MEUS or Sham ultrasound (US), respectively. MEUS was induced by Sonazoid microbubble and a focused therapeutic US device. Contrast-enhanced ultrasound (CEUS) was used to assess tumor perfusion before and after treatment. Microvessel density (MVD) was evaluated with immunohistochemical staining of CD31, CD34, and VEGFA. TUNEL assay was used to determine the apoptosis rate of tumor cells. Results Endostar + MEUS combined group induced the most reduced blood perfusion and most retarded tumor growth compared with other 3 groups. Decreased MVD was shown in Endostar + MEUS, Endostar and MEUS group, but the lowest MVD value was presented in the combined treatment group. Significant increase was observed in the combined therapy group and MEUS group. Conclusions This study showed an improved anti-vascular and anti-angiogenic effect achieved by combining Endostar and MEUS, and may provide a new method potential for anti-tumor therapy.