Ultrasound-stimulated microbubbles enhances radiosensitivity of ovarian cancer

Abstract

Background Radiation therapy is regarded as an effective treatment for early ovarian cancer (OC). However, due to radiation resistance caused by DNA double-strand breaks (DSBs) and angiogenesis, the efficacy of radiotherapy for advanced OC is limited and controversial. Purpose To explore whether ultrasound-stimulated microbubbles (USMBs) can enhance the radiosensitivity of OC. Material and Methods OC cells (ES-2) were respectively irradiated with 5-Gy and 10-Gy radiation doses with or without exposure to USMB. Methyl thiazolyltetrazolium (MTT) and colony-formation assays were conducted to detect the viability and proliferation of ES-2 cells after USMBs and ionizing radiation (IR) treatment. Immunofluorescence assays were conducted to examine levels of gamma-H2A histone family member X (γ-H2AX), an indicator for DSBs. Flow cytometry analyses were carried out to assess the apoptosis of ES-2 cells. The angiogenic activity of human umbilical vein endothelial cells (HUVECs) was measured by tube formation assays. Results USMBs enhanced IR-induced suppressive effect on the viability and proliferation of OC cells. The protein levels of phosphorylated γ-H2AX and CHK1 were significantly upregulated after IR treatment and further enhanced by USMBs. In addition, USMBs enhanced the promotion of IR-mediated OC cell apoptosis. The inhibitory effect of IR on angiogenesis was further enhanced by USMBs, and protein levels of AT1R, VEGFA, and EGFR were downregulated by IR in a dose-dependent way and then enhanced by USMB treatment in HUVECs. Conclusions USMB exposure significantly enhances the radiosensitivity of OC by suppressing cell proliferation, promoting OC cell apoptosis, and inhibiting angiogenesis.