Department of Orthopedics, Linyi Central Hospital, Linyi, Shandong 276000, China.
Department of Thyroid Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, China.
Curr Pharm Biotechnol. 2020;21(2):131-139. doi: 10.2174/1389201020666190821151120.
The aim of the study was to investigate the expression of sCLU in relation to the clinicopathological features and prognosis of patients with untreated High-Grade Osteosarcoma (HGOS) and to evaluate sCLU as a target for osteosarcoma (OS) therapies.
The expression of sCLU in 98 patients of HGOS enrolled from April 2005 to March 2015 at the affiliated hospital of Qingdao University was evaluated by immunohistochemistry. The sCLU expression, clinical data and survival were compared. siRNA-mediated sCLU gene silencing on cell apoptosis, viability, invasion and chemosensitivity to doxorubicin in U2OS cells in vitro was evaluated.
sCLU expression was found in 59 (60%) of the 98 patients. A positive correlation was observed between sCLU expression and metastatic disease (P = 0.036) and a negative correlation between sCLU expression and response to chemotherapy (P = 0.002). Targeting sCLU expression in U2OS cells induced significant reduction in cellular growth and higher rates of spontaneous endogenous apoptosis. In addition, targeting sCLU expression inhibited the invasion of U2OS cells. Furthermore, targeting sCLU expression significantly sensitized to chemotherapeutic drug, doxorubicin.
The overexpression of sCLU was significantly correlated with metastasis and chemosensitivity in patients with HGOS. sCLU may be a promising therapeutic or chemopreventive target for human OS treatment.
本研究旨在探讨未治疗的高级别骨肉瘤（HGOS）患者中 sCLU 的表达与临床病理特征和预后的关系，并评估 sCLU 作为骨肉瘤（OS）治疗靶点的可能性。
采用免疫组织化学法检测 2005 年 4 月至 2015 年 3 月在青岛大学附属医院就诊的 98 例 HGOS 患者中 sCLU 的表达情况，比较 sCLU 表达、临床资料与生存情况。采用 siRNA 介导的 sCLU 基因沉默技术，体外评估 U2OS 细胞中 sCLU 基因沉默对细胞凋亡、活力、侵袭和对阿霉素化疗敏感性的影响。
98 例患者中 59 例（60%）表达 sCLU。sCLU 表达与转移疾病呈正相关（P = 0.036），与化疗反应呈负相关（P = 0.002）。U2OS 细胞中 sCLU 表达的靶向作用导致细胞生长显著减少，自发内源性凋亡率升高。此外，靶向 sCLU 表达抑制了 U2OS 细胞的侵袭。此外，靶向 sCLU 表达显著增加了对化疗药物阿霉素的敏感性。
sCLU 的过表达与 HGOS 患者的转移和化疗敏感性显著相关。sCLU 可能是治疗人类 OS 的一种有前途的治疗或化学预防靶点。
