Objective. To determine if microbubble-mediated ultrasound therapy (MB-UST) can improve cisplatin or cetuximab cytotoxicity of head and neck squamous cell carcinoma (HNSCC) in vitro and in vivo by increasing tumor-specific drug delivery by disruption of tumor cell membranes and enhancing vascular permeability.Study Design. In vitro and in vivo study.Setting. University medical center.Subjects. Immunodeficient mice (6 weeks old) and 4 HNSCC cell lines.Methods. Changes to cell permeability were assessed in vitro after MB-UST. Cellular apoptosis resulting from adjuvant MB-UST with subtherapeutic doses of cisplatin or cetuximab was assessed by cell survival assays in vitro. The in vivo effect of adjuvant MB-UST in flank tumors was assessed in vivo with histological analysis and diffusion-weighted magnetic resonance imaging (DW-MRI).Results. In vitro results revealed that MB-UST can increase cell permeability and enhance drug uptake and apoptosis in 4 HNSCC cell lines. In vivo adjuvant MB-UST with cetuximab or cisplatin showed a statistically significant reduction in tumor size when compared with untreated controls. TUNEL analysis yielded a larger number of cells undergoing apoptosis in tumors treated with cetuximab and adjuvant MB-UST than did cetuximab alone but was not significantly greater in tumors treated with cisplatin and adjuvant MB-UST compared with cisplatin alone. DW-MRI analysis showed more free water, which corresponds to increased cell membrane disruption, in tumors treated with MB-UST.Conclusion. MB-UST promotes disruption of cell membranes in tumor cells in vitro, which may be leveraged to selectively improve the uptake of conventional and targeted therapeutics in vivo.
|Number of pages
|Otolaryngology - Head and Neck Surgery (United States)
|Published - Jun 2012
- head and neck squamous cell carcinoma
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