Department of Hand and Foot Repair and Reconstruction Surgery, Dezhou People's Hospital, 253000, Dezhou, China.
Department of Joint Surgery, Dezhou People's Hospital, 253000, Dezhou, China.
Dokl Biochem Biophys. 2020 Nov;495(1):354-360. doi: 10.1134/S1607672920060022. Epub 2020 Dec 25.
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 × 10 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.
成骨肉瘤是一种高发于青少年和年轻人的恶性骨肿瘤。本研究探讨了靛玉红-3'-肟（IDR3O）衍生物在体外对骨肉瘤细胞增殖和体内肿瘤生长的影响。采用 WST-8 和 TUNEL 染色法评估骨肉瘤细胞生长变化和凋亡诱导。IDR3O 处理 MG63 和 Saos-2 细胞可抑制增殖、激活凋亡并促进 AMPK 激活。与对照组（未处理）细胞相比，IDR3O 处理的 MG63 和 Saos-2 细胞中 PGC-1α（过氧化物酶体增殖物激活受体-γ 共激活物-1α）水平明显升高。在通过背部皮下植入 2×10 MG63 细胞诱导骨肉瘤的小鼠模型中，实验组在 45 天内通过腹腔内给予 IDR3O。与对照组（未处理）相比，IDR3O 治疗显著抑制了肿瘤的发展，但体重没有变化。IDR3O 通过 AMPK 依赖性途径抑制骨肉瘤细胞生长并激活凋亡。因此，IDR3O 可考虑用于治疗骨肉瘤，因为它可有效抑制小鼠肿瘤生长。
