In Vitro, In Vivo and Ex Vivo Irradiation Research of Low-frequency Ultrasound Combined with Chemotherapy for Ovarian Carcinoma Cells.

INTRODUCTION

To investigate the effects of 20 kHz low-frequency ultrasound irradiation-mediated microbubbles (USMB) combined with chemotherapy paclitaxel and cisplatin (PC) on ovarian cancer cells.

METHODS

In the in vitro research, ovarian cancer cell lines were divided into four groups: control, USMB, PC, and USMB+PC. The cell membrane structure was observed using scanning electron microscopy (SEM). A TUNEL assay was used to investigate cell apoptosis. In the in vivo study, USMB+PC was used to treat the ascites in the nude mice. The ascites volumes were calculated by magnetic resonance imaging. In the ex vivo research, ascites samples of clinical ovarian cancer patients were collected and focused with USMB+PC and observed by liquid-based cytology.

RESULTS

SEM revealed cell wall defects in the USMB and USMB+PC, with pores ranging from 5 to 15 μm in diameter. The USMB+PC had the highest apoptosis rate, with statistical differences compared to the other three groups (all p<0.05). After USMB+PC treatment, the volume of ascites in the nude mice decreased (t=3.6, p=0.0228). In the USMB+PC, tumour cells in the ascites showed obvious degeneration and necrosis.

DISCUSSION: The mechanism is that US irradiation causes MBs to rupture, generating shock waves, damaging tumor cell walls, forming pores (sonoporation), leading to more drugs entering cancer cells. The clinical significance of this technology is that it can increase the dosage of locally targeted tumor cells, reduce systemic chemotherapy use/or the clinical dosage of chemotherapy drugs, and decrease the toxic side effects on normal tissue cells. The limitation is that there are relatively few cases of patients with ex vivo ascites. Future research direction is US irradiation on ex vivo ascites of ovarian cancer patients with different histological types.

CONCLUSION

US cavitation and chemotherapy inhibit ovarian cancer cells.