Abstract

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.

中文翻译：

---

Indirubin-3'-肟（IDR3O）通过AMPK激活和PGC-1α/ TFAM上调抑制骨肉瘤细胞的体外增殖和体内肿瘤的生长

摘要

骨肉瘤是骨骼的恶性肿瘤，在青少年和年轻人中发病率很高。本研究研究了靛玉红3'-肟（IDR3O）衍生物对骨肉瘤细胞体外增殖和体内肿瘤生长的影响。使用WST-8和TUNEL染色测定法评估骨肉瘤细胞的生长变化和诱导的凋亡。用IDR3O处理MG63和Saos‑2细胞可抑制增殖，激活细胞凋亡并促进AMPK激活。与未处理的对照细胞相比，在IDR3O处理的MG63和Saos‑2细胞中，PGC-1α（过氧化物酶体增殖物激活的受体-γ共激活剂-1α）水平得到了显着提高。在小鼠模型中，通过植入2×10 ⁶诱导骨肉瘤MG63细胞位于皮下背侧。然后，实验组小鼠在45天内腹膜内接受IDR3O。与对照组（未治疗）相比，IDR3O治疗显着抑制了肿瘤的发展，但并未改变体重。IDR3O通过AMPK依赖性途径抑制骨肉瘤细胞生长并激活细胞凋亡。因此，IDR3O可以考虑用于治疗骨肉瘤，因为它可以有效抑制小鼠的肿瘤生长。