Cell apoptosis and proliferation inhibition of pancreatic cancer induced by sub-threshold focused ultrasound (FUS)

Abstract

Objective: To evaluate the effects of sub-threshold focused ultrasound (FUS) sonication on the pancreatic cancer cell.

Materials and methods: The human pancreatic carcinoma cell line PaTu 8988t suspension and pancreatic carcinoma xenograft in nude mice were sonicated by FUS using sub-threshold doses. The temperature at the focus was controlled at below 60°C. The cell apoptosis in vitro was tested by flow cytometer at 3, 6, 12, 24 and 48h after FUS sonication. Colony formation was used to evaluate the cell growth inhibition of FUS in vitro. The tumor volume of the xenograft was measured before and after FUS sonication. Then the slides of the tumor were under hematoxylin-eosin (H&E) staining and TdT-mediated dUTP nick end labeling (TUNEL) to evaluate the effect of FUS on pancreatic carcinoma xenograft in vivo.

Results: The maximum cell suspension temperature of the FUS sonication group was 55.8±2.17°C. The cell apoptosis rate peaked at 24h after FUS sonication, the differences between the FUS sonication group and control group were statistically significant (P<0.05). Colony formation rates were 50.40±3.81% for the control group and 26.82±2.88% for FUS sonication group (P<0.05). For the xenografts in nude mice, the mean tumor volumes of the control group and the FUS sonication group 15 days after sonication were 1746.58±312.77mm(3) and 1085.23±217.13mm(3) (P<0.05). H&E staining and TUNEL assay showed both necrotic and apoptotic cells.

Conclusion: Sub-threshold FUS sonication could induce cell apoptosis and inhibit the proliferation of pancreatic cancer cells.