Metadherin (MTDH), also known as astrocyte-elevated gene-1, was first cloned in 2002 and has been confirmed as an oncogene in numerous types of cancer by previous studies. Overexpression of MTDH has been observed in multiple types of cancer, including breast, esophageal, prostate, cervical and non-small-cell lung cancer, as well as neuroblastoma and hepatocellular carcinoma. However, at present, few investigations into MTDH‑associated prostate cancer have been performed. A previous study suggested that MTDH was expressed at higher levels in prostate cancer samples, compared with those of benign prostatic hyperplasia. The present study aimed to elucidate the effects of MTDH as an oncogene associated with the biological behavior of prostate cancer cells and chemotherapy-sensitivity to cisplatin in vitro. It was demonstrated that the inhibition of MTDH expression promoted cell apoptosis, reduced cell viability and weakened the invasive ability of prostate cancer cells. In addition, the suppression of MTDH expression increased cell sensitivity to cisplatin. Furthermore, it was demonstrated that MTDH‑associated phosphoinositide 3-kinase/Akt signaling pathways may be involved in mediating the biological behavior of prostate cancer.