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The present study aimed to investigate the effects of cold atmospheric plasma (CAP)‑activated Ringer's solution on osteosarcoma cell lines MG63 and U2OS, and to identify the molecular mechanism underlying these effects. CAP‑activated Ringer's solution was used to treat osteosarcoma cell lines MG63 and U2OS for 30 min. Cell viability was measured using the MTT method. The apoptosis rate was detected using Annexin‑V and propidium iodide. The expression levels of cytochrome c, caspase‑3 and polyADP ribose polymerase (PARP) in MG63 cells wer