Modulation of cell viability, apoptosis, and autophagy in pancreatic cancer cells using therapeutic ultrasound with microbubbles and gemcitabine.

Abstract

Purpose: This study aimed to investigate the effects of therapeutic ultrasound (TUS) combined with microbubbles and gemcitabine on cell viability, apoptosis, and autophagy in pancreatic cancer cells. The goal was to elucidate the cell death mechanisms by which TUS enhances drug delivery and therapeutic efficacy.

Methods: Human pancreatic ductal adenocarcinoma CFPAC-1 cells were treated with varying TUS intensities (0.29 MPa/continuous wave, 0.42 MPa/50% duty cycle, and 0.86 MPa/10% duty cycle), microbubble volumes (0, 10, and 50 μL), and gemcitabine concentrations (0 μg/mL and 2 μg/mL). Cell viability was assessed by MTT assay, apoptosis by annexin V/propidium iodide staining and flow cytometry, and autophagy by an autophagy detection kit. Statistical analyses included three-way analysis of variance and post hoc Tukey honestly significant difference tests to evaluate the effects and interactions of treatment variables.

Results: TUS combined with microbubbles and gemcitabine significantly reduced cell viability, induced apoptosis, and modulated autophagy in pancreatic cancer cells. Higher ultrasound intensities (with lower duty cycles) and increased microbubble volumes further enhanced these effects. Autophagy activation varied across treatment conditions. Under certain parameters, autophagy exhibited dose-dependent suppression with higher-intensity TUS, thereby promoting apoptosis-mediated cell death.

Conclusion: TUS combined with microbubbles and gemcitabine synergistically induces cell death in pancreatic cancer cells through mechanical bioeffects and enhanced drug delivery, mediated by both apoptosis induction and autophagy modulation. These findings highlight a promising strategy for improving pancreatic cancer treatment outcomes, warranting further in vivo and clinical studies to optimize parameters and assess translational potential.