Therapeutic effects of microbubbles added to combined high-intensity focused ultrasound and chemotherapy in a pancreatic cancer xenograft model

Abstract

Objective: To investigate whether high-intensity focused ultrasound (HIFU) combined with microbubbles enhances the therapeutic effects of chemotherapy.

Materials and Methods: A pancreatic cancer xenograft model was established using BALB/c nude mice and luciferase-expressing human pancreatic cancer cells (PANC-1). Mice were randomly assigned to five groups according to treatment: control (n = 10), gemcitabine alone (GEM, n = 12), HIFU with microbubbles (HIFU+MB, n = 11), combined HIFU and gemcitabine (HIGEM, n = 12), and HIGEM+MB (n = 13). After three weekly treatments, apoptosis rates were evaluated using the TUNEL assay in two mice per group. Tumor volume and bioluminescence were monitored using high-resolution 3D ultrasound imaging and in vivo bioluminescence imaging for eight weeks in the remaining mice.

Results: The HIGEM+MB group showed significantly higher apoptosis rates than the other groups (p < 0.05) and exhibited the slowest tumor growth. From week 5, the tumor-volume-ratio relative to the baseline tumor volume was significantly lower in the HIGEM+MB group than in the control, GEM, and HIFU+MB groups (p < 0.05). Despite visible distinction, the HIGEM and HIGEM+MB groups showed no significant differences.

Conclusion: HIFU combined with microbubbles enhances the therapeutic effects of gemcitabine chemotherapy in a pancreatic cancer xenograft model.