0100485180

open access

Accepted Manuscript

Proapoptotic effect of nonthermal pulsed ultrasound on prostate cancer cells in a nude mouse model

English (英語)

The Prostate

83(12)

1217-1226

John Wiley & Sons

2023-09

2024-05-23

Background: Ultrasound (US) can induce cell injury, and we have previously reported that adjusting the pulse repetition frequency (PRF) of ultrasound output can induce prostate cancer cell destruction without causing a rise in the temperature of the irradiated area. In this study, we examined the mechanism of nonthermal ultrasound cell destruction, which was not fully clarified in our previous reports. Methods: In vitro, we evaluated postirradiation cells immediately after treatment and examined membrane disruption by proliferation assay, LDH assay, and apoptosis assay. In vivo, we injected mice with human LNCaP and PC-3 prostate cancer cells and evaluated the therapeutic effects of US irradiation by H-E staining and immunostaining. Results: Proliferation assays showed inhibition at 3 h postirradiation independently of PRF and cell line (p < 0.05). Quantitative assessment of apoptosis/necrosis by flow cytometry showed widely varying results depending on cell type. LNCaP showed an increase in late apoptosis at 0 h independent of PRF (p < 0.05), while PC-3 showed no significant difference at 0 h. The LDH assay showed an increase in LDH independent of PRF in LNCaP (p < 0.05 respectively), but no significant difference in PC-3. In vivo, tumor volume was compared and a significant reduction was observed at 10 Hz for LNCaP (p < 0.05) and 100 Hz for PC-3 (p < 0.001) at 3 weeks after the start of irradiation. The excised tumors were evaluated with Ki-67, Caspase-3, and CD-31 and showed a significant treatment effect independent of cell type and PRF (p < 0.001 respectively). Conclusion: Examining the mechanism behind the therapeutic effect of US irradiation revealed that the main effect was achieved by apoptosis induction rather than necrosis.

ultrasound irradiation

学術雑誌論文

This is the peer reviewed version of the following article: [Maeda, K, Shigemura, K, Hayashi, F, et al. Proapoptotic effect of nonthermal pulsed ultrasound on prostate cancer cells in a nude mouse model. The Prostate. 2023; 83: 1217-1226.], which has been published in final form at [https://doi.org/10.1002/pros.24581]. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. This article may not be enhanced, enriched or otherwise transformed into a derivative work, without express permission from Wiley or by statutory rights under applicable legislation. Copyright notices must not be removed, obscured or modified. The article must be linked to Wiley’s version of record on Wiley Online Library and any embedding, framing or otherwise making available the article or pages thereof by third parties from platforms, services and websites other than Wiley Online Library must be prohibited.