Ultrasound Therapy Boosts Drug Toxicity In Vitro and In Vivo

Abstract

Objective: Ultrasound-mediated therapy (UST) utilizes mechanical vibration of microbubble contrast agent to enhance cell permeability and anti-cancer drug delivery. Here we determine if UST can improve cisplatin or cetuximab treatment of HNSCC in vitro and in vivo.

Method: Cell permeability was assessed after UST in four HNSCC cell lines (SCC1, SCC5, Cal27, and FaDu). Combination of UST with cisplatin or cetuximab was assessed by cell survival in vitro. In vivo effects on flank tumors were measured in immune-suppressed mice.

Results: Cell permeability was 48.2 ± 4.8% greater in cells treated with UST compared to controls (P in vitro, UST alone had no effect on cell survival (P = .59), but combination treatment with cetuximab (P = .002) or cisplatin (P in vivo) (P = .81), but combination with cetuximab (P = .04) orcisplatin (P = .01) enhanced their antitumor effects. TUNEL analysis of flank tumors demonstrated increased apoptosis in UST+ cetuximab (55% vs 44%, P = .05), and UST+ cisplatin (84% vs 77%, P = .24) compared with monotherapy with either drug.

Conclusion: The antitumor effects of cetuximab and cisplatin in HNSCC are enhanced by concurrent treatment with ultrasound-mediated therapy in vitro and in vivo.