Carbon-ion beam irradiation combined with miR-17-5p/miR-17-3p inhibitors effectively kill osteosarcoma cells.

Osteosarcoma (OS) is the most common type of bone cancer and is highly resistant to conventional photon beam radiotherapy; however, carbon-ion radiotherapy (CIRT) is effective in treating OS. In this study, to investigate whether miR-17-5p/miR-17-3p inhibitors act as radiosensitizers for CIRT, U2OS and MG63 OS cells were treated with carbon-ion beam irradiation (IR) alone, X-ray IR alone, or with one of the IR treatments in combination with miR-17-3p inhibitors. Cell death and invasive and migratory abilities were analyzed using cell viability and cell Transwell migration and invasion assays. Apoptosis and autophagy-related protein expression and DNA double-strand break (DSB) induction was determined using western blotting and immunofluorescence staining. We found that carbon-ion beam IR combined with miR-17-5p/miR-17-3p inhibitors significantly inhibited OS cell proliferation, migration, and invasion and markedly increased apoptosis-related cleaved-caspase 3, cleaved-PARP expression compared to carbon-ion beam IR and X-ray IR alone. Furthermore, carbon-ion beam IR combined with miR-17-5p/miR-17-3p inhibitors markedly promoted autophagy induction. In addition, combination treatment with miR-17-5p/miR-17-3p inhibitors and carbon-ion beam IR significantly increased the number of γH2AX foci as well as its phosphorylation. Taken together, miR-17-5p/miR-17-3p inhibitors enhanced the carbon-ion beam radiosensitivity of OS cells, presenting a novel strategy for the development of carbon-ion beam combination therapy.