Objective: To assess the effects of vascular-disrupting agent (VDA)-based therapy including monitoring of therapeutic efficacy with contrast-enhanced ultrasound (CEUS) in a gastric cancer model.
Materials & methods: Gastric cancer cell lines and endothelial cells were used. Effects of the VDA ASA404 on cells were determined by MTT assays and Western blotting in vitro. Therapeutic efficacy of ASA404 was assessed in vivo in a subcutaneous mouse model in combination with paclitaxel. CEUS with TIC (time intensity curve) analyses was employed to measure tumor perfusion. Finally, tumor tissue was harvested and processed for histological work-up.
Results: In vitro, ASA404 impaired growth of ECs upon stimulation with conditioned media from gastric cancer cells. No direct effects on tumor cells were observed. In vivo treatment with ASA404 in combination with paclitaxel led to significant decrease of tumor microvascularization as determined by CEUS. Furthermore, combination of ASA404 with paclitaxel showed a significant inhibition of tumor growth which was paralleled by strong reduction of tumor cell proliferation and vessel area.
Conclusion: VDA-based therapy in combination with paclitaxel, and therapy monitoring by CEUS, appears to be a promising strategy for gastric cancer.