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氯化镉通过降低 FOXM1 表达增强骨肉瘤细胞对顺铂的敏感性。

Cadmium chloride enhances cisplatin sensitivity in osteosarcoma cells by reducing FOXM1 expression.

机构信息

Department of Spine Surgery, The Affiliated Yuebei People's Hospital of Shantou University Medical College, Shaoguan, Guangdong 512025, P.R. China.

Department of Orthopedics, Zhujiang Hospital, Southern Medical University, Guangzhou, Guangdong 510280, P.R. China.

出版信息

Oncol Rep. 2020 Aug;44(2):650-660. doi: 10.3892/or.2020.7632. Epub 2020 Jun 4.

Abstract

Osteosarcoma is a highly malignant disease and is associated with a poor patient prognosis and a high mortality rate. Disease prognosis significantly correlates with chemotherapeutic responses. Cadmium is a heavy metal with specific effects on bone, but its benefits for osteosarcoma treatment have not been characterized. In the present study, cadmium chloride was used to treat MG63 osteosarcoma cells, and their gene expression profiles were assessed by GeneChip technology. We found that forkhead box protein M1 (FOXM1) was downregulated by cadmium chloride, and lentiviral‑mediated silencing of FOXM1 confirmed a role for this factor in the cisplatin resistance of MG63 cells. In nude mice, cadmium chloride enhanced the sensitivity of osteosarcoma to cisplatin, an effect mediated by FOXM1. Collectively, these data indicate that cadmium chloride can alter the sensitivity of osteosarcoma cells to cisplatin through FOXM1, highlighting it as a potential therapeutic target and prognostic factor for osteosarcoma.

摘要

骨肉瘤是一种高度恶性的疾病,与患者预后不良和死亡率高相关。疾病预后与化疗反应密切相关。镉是一种对骨骼有特殊作用的重金属,但它在骨肉瘤治疗中的益处尚未得到阐明。在本研究中,氯化镉被用于治疗 MG63 骨肉瘤细胞,并通过 GeneChip 技术评估其基因表达谱。我们发现,叉头框蛋白 M1 (FOXM1) 被氯化镉下调,FOXM1 的慢病毒介导沉默证实了该因子在 MG63 细胞顺铂耐药中的作用。在裸鼠中,氯化镉通过 FOXM1 增强了骨肉瘤对顺铂的敏感性。综上所述,这些数据表明,氯化镉可以通过 FOXM1 改变骨肉瘤细胞对顺铂的敏感性,提示其可能成为骨肉瘤的潜在治疗靶点和预后因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/30b3/7336512/d363d078cc68/OR-44-02-0650-g00.jpg

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