Department of Nuclear Medicine; Changhai Hospital of Shanghai, Shanghai 200433, P.R. China.
Geriatric Department, China‑Japan Union Hospital of Jilin University, Changchun, Jilin 130033, P.R. China.
Mol Med Rep. 2019 Mar;19(3):1571-1580. doi: 10.3892/mmr.2018.9774. Epub 2018 Dec 18.
Osteosarcoma is the most common type of primary malignant bone tumor, with extremely poor prognosis in patients with metastatic disease and resistance to therapy, such as multidrug regimens. The mechanisms of drug resistance are quite complex and have not been fully elucidated; thus, novel therapeutic targets should be identified to alleviate drug resistance in osteosarcoma. In the present study, the transcriptomes of the human osteosarcoma cell line MG63 and vincristine (VCR)‑resistant MG63 cells were compared by microarray analysis. A total of 1,300 genes (602 upregulated and 698 downregulated) were reported to be differentially expressed in MG63/VCR compared with MG63 cells. Bioinformatics analysis predicted that the differentially expressed genes were mainly enriched in the B cell receptor, UVA‑induced mitogen‑activated protein kinases and receptor tyrosine kinase 2/3 signaling pathways. In the present study, 10 of the dysregulated genes, including roundabout homolog 1, death‑associated protein kinase 1 and A‑kinase anchor protein 12 were further evaluated by reverse transcription‑quantitative polymerase chain reaction. These results may aid the validation of candidate biomarkers for the treatment and prognosis of osteosarcoma, and provide novel insight into the molecular mechanisms underlying the drug resistance of osteosarcoma cells.
骨肉瘤是最常见的原发性恶性骨肿瘤,转移性疾病患者的预后极差,对多药治疗方案等治疗具有耐药性。耐药机制非常复杂,尚未完全阐明;因此,应该确定新的治疗靶点,以减轻骨肉瘤的耐药性。在本研究中,通过微阵列分析比较了人骨肉瘤细胞系 MG63 和长春新碱(VCR)耐药 MG63 细胞的转录组。与 MG63 细胞相比,报告共有 1300 个基因(602 个上调和 698 个下调)在 MG63/VCR 中差异表达。生物信息学分析预测,差异表达的基因主要富集在 B 细胞受体、UVA 诱导的有丝分裂原激活蛋白激酶和受体酪氨酸激酶 2/3 信号通路中。在本研究中,进一步通过逆转录-定量聚合酶链反应评估了 10 个失调基因,包括绕路同源物 1、死亡相关蛋白激酶 1 和 A 激酶锚蛋白 12。这些结果可能有助于验证骨肉瘤治疗和预后的候选生物标志物,并为骨肉瘤细胞耐药的分子机制提供新的见解。