Department of Orthopedics, Rizhao People's Hospital, Rizhao, Shandong 276826, P.R. China.
Department of Neurosurgery, Rizhao People's Hospital, Rizhao, Shandong 276826, P.R. China.
Mol Med Rep. 2017 Dec;16(6):8542-8548. doi: 10.3892/mmr.2017.7629. Epub 2017 Sep 26.
Osteosarcoma is the most common type of bone cancer, and accounts for ~3% of cancers that occurring in children. Chondromodulin‑I (ChM-I) is a 25 kDa glycoprotein that is expressed mainly in cartilage. ChM-I demonstrates anti‑angiogenic activity and has been suggested to inhibit endothelial cells from invading cartilage, and then has been shown to be an inhibitor of tumorigenesis. However, it remains unclear if ChM‑I has any direct anti‑tumorigenesis role on osteosarcoma. Therefore, the present study aimed to identify whether ChM‑I has any direct inhibit effect on human osteosarcoma cells. A bromodeoxyuridine incorporation assay was performed on the Saos‑2 human osteosarcoma cell line treated with or without recombinant human ChM‑I, to evaluate its impact on DNA synthesis. An adenovirus carrier for the expression of ChM‑I was constructed and transfected into tumor cells in vitro to evaluate the effect of ChM‑I on tumor cells. Additionally, ChM‑I was knocked down by using small interfering RNA to downregulate the expression of ChM‑I. Cell invasion, migration and cell‑colony formation assays, and xenograft tumor experiments were performed to evaluate the effects of ChM‑I on tumor cells in vitro and in vivo. The results demonstrated that ChM‑I could suppress DNA synthesis of human osteosarcoma cells, and it also exerted an inhibitory effect on the proliferation and colony formation abilities of human osteosarcoma cells. In addition, ChM‑I inhibited cell invasion and migration in vitro and suppressed osteosarcoma cell growth significantly in vivo. In conclusion, ChM‑I directly suppressed the proliferation and growth of osteosarcoma cells in an anchorage‑independent manner, and may therefore be a promising drug for the treatment of osteosarcoma.
骨肉瘤是最常见的骨癌类型,约占儿童癌症的 3%。软骨调节素 I(ChM-I)是一种 25kDa 的糖蛋白,主要在软骨中表达。ChM-I 具有抗血管生成活性,并被认为可抑制内皮细胞侵入软骨,随后被证明是肿瘤发生的抑制剂。然而,ChM-I 是否对骨肉瘤具有直接的抗肿瘤作用仍不清楚。因此,本研究旨在确定 ChM-I 是否对人骨肉瘤细胞具有直接的抑制作用。通过溴脱氧尿苷掺入试验,检测重组人 ChM-I 处理的 Saos-2 人骨肉瘤细胞系对 DNA 合成的影响。构建了表达 ChM-I 的腺病毒载体,并在体外转染肿瘤细胞,以评估 ChM-I 对肿瘤细胞的作用。此外,通过使用小干扰 RNA 敲低 ChM-I 的表达来下调 ChM-I 的表达。进行了细胞侵袭、迁移和细胞集落形成试验以及异种移植肿瘤实验,以评估 ChM-I 对体外和体内肿瘤细胞的影响。结果表明,ChM-I 可抑制人骨肉瘤细胞的 DNA 合成,对人骨肉瘤细胞的增殖和集落形成能力也具有抑制作用。此外,ChM-I 抑制体外细胞侵袭和迁移,并显著抑制体内骨肉瘤细胞生长。综上所述,ChM-I 可直接抑制骨肉瘤细胞的增殖和生长,具有独立于锚定的方式,因此可能成为治疗骨肉瘤的有前途的药物。