Focused ultrasound radiosensitizes human cancer cells by enhancement of DNA damage

Purpose High-intensity focused ultrasound (HIFU/FUS) has expanded as a noninvasive quantifiable option for hyperthermia (HT). HT in a temperature range of 40-47 degrees C (thermal dose CEM43 >= 25) could work as a sensitizer to radiation therapy (RT). Here, we attempted to understand the tumor radiosensitization effect at the cellular level after a combination treatment of FUS+RT. Methods An in vitro FUS system was developed to induce HT at frequencies of 1.147 and 1.467 MHz. Human head and neck cancer (FaDU), glioblastoma (T98G), and prostate cancer (PC-3) cells were exposed to FUS in ultrasound-penetrable 96-well plates followed by single-dose X-ray irradiation (10 Gy). Radiosensitizing effects of FUS were investigated by cell metabolic activity (WST-1 assay), apoptosis (annexin V assay, sub-G1 assay), cell cycle phases (propidium iodide staining), and DNA double-strand breaks (gamma H2A.X assay). Results The FUS intensities of 213 (1.147 MHz) and 225 W/cm(2) (1.467 MHz) induced HT for 30 min at mean temperatures of 45.20 +/- 2.29 degrees C (CEM43 = 436 +/- 88) and 45.59 +/- 1.65 degrees C (CEM43 = 447 +/- 79), respectively. FUS improves the effect of RT significantly by reducing metabolic activity in T98G cells 48 h (RT: 96.47 +/- 8.29%; FUS+RT: 79.38 +/- 14.93%; p = 0.012) and in PC-3 cells 72 h (54.20 +/- 10.85%; 41.01 +/- 11.17%; p = 0.016) after therapy, but not in FaDu cells. Mechanistically, FUS+RT leads to increased apoptosis and enhancement of DNA double-strand breaks compared to RT alone in T98G and PC-3 cells. Conclusion Our in vitro findings demonstrate that FUS has good potential to sensitize glioblastoma and prostate cancer cells to RT by mainly enhancing DNA damage.

Automated summary

High-intensity focused ultrasound shows potential in sensitizing glioblastoma and prostate cancer cells to radiation therapy by enhancing DNA damage.