Experimental study on synergistic inhibition of tumor growth by microbubble cavitation induced by low intensity ultrasound combined with hemocoagulase and Endostar / 中华超声影像学杂志

ABSTRACT

Objective:To investigate the synergistic effect of physical intervention and chemotherapeutic drug therapy on tumor growth by blocking tumor microvessels and injecting chemotherapy drug Endostar (ecombinant human vascular endostatin injection) to inhibit tumor neovascularization by low intensity ultrasound induced microbubble cavitation combined with hemocoagulase.Methods:Seventy-five male NU/NU mice bearing human-derived lung adenocarcinoma, weighing 25-30 g, were randomly divided into microbubble-enhanced ultrasonic cavitation+ Endostar group (MEUC+ Endostar), microbubble-enhanced ultrasonic cavitation+ hemocoagulase+ Endostar group (MEUC+ HC+ Endostar), microbubble-enhanced ultrasonic cavitation (MEUC), Endostar group (Endostar) and sham group. Fifteen mice in each group were given the corresponding treatment intervention for 4 consecutive days followed by 4 days of aseptic feeding. Two-dimensional ultrasound and contrast-enhanced ultrasound (CEUS) were performed before intervention, immediately after intervention and 4 days after intervention, respectively. Tumor tissues were obtained for vascular endothelial growth factor immunofluorescence staining, and microvessel density (MVD) was observed.Results:There was no difference in tumor volume between the groups before the intervention ( P>0.05). Immediately after the intervention, filling defects were observed in MEUC+ Endostar group, MEUC+ HC+ Endostar group and MEUC group, while filling was good in Endostar group and sham group; 4 days after the intervention, filling defects were observed in MEUC+ Endostar group and MEUC+ HC+ Endostar group. The filling defect was still present in Endostar group, while partial recovery of perfusion was performed in MEUC group, and PI and AUC were still significantly lower in MEUC+ HC+ Endostar group than in the other groups ( P<0.05). When tumor tissues were obtained 4 days after the intervention, the MVD in MEUC+ HC+ Endostar group was significantly lower than that in the remaining groups, and the difference of MVD in tumor tissue was statistically significant ( P<0.05). Conclusions:Low intensity ultrasound induced microbubble cavitation combined with hemocoagulase and Endostar can produce a synergistic effect in blocking tumor microvessels and inhibiting tumor angiogenesis, which can more effectively inhibit tumor growth.