Indirubin-3'-Oxime (IDR3O) Inhibits Proliferation of Osteosarcoma Cells in vitro and Tumor Growth in vivo Through AMPK-Activation and PGC-1α/TFAM Up-Regulation.

Osteosarcoma, a malignant tumor of bones, has very high incidence in adolescents and young people. The present study investigated the effect of indirubin-3'-oxime (IDR3O) derivative on proliferation of osteosarcoma cells in vitro and tumor growth in vivo. Changes in growth and induction of apoptosis in osteosarcoma cells were assessed using WST-8 and TUNEL staining assays. Treatment of MG63 and Saos‑2 cells with IDR3O inhibited proliferation, activated apoptosis and promoted AMPK-activation. In IDR3O treated MG63 and Saos‑2 cells PGC-1α (Peroxisome proliferator-activated receptor-γ coactivator-1α) levels were markedly promoted compared to control (untreated) cells. In the mice model osteosarcoma was induced by implantation of 2 × 106 MG63 cells on dorsal side subcutaneously. Then the experimental group of mice received IDR3O intra-peritoneally during 45 days. IDR3O-treatment suppressed tumor development significantly compared to control (untreated) group but didn't changed body weight. IDR3O inhibits osteosarcoma cell growth and activates apoptosis through AMPK dependent pathway. Therefore, IDR3O may be considered for treatment of osteosarcoma as it effectively arrests tumor growth in mice.