Li Fusheng, Xu Jia, Zhu Yue, Sun Liang, Zhou Renyi
Department of Orthopaedics, The First Affiliated Hospital of China Medical University, Shenyang, People's Republic of China.
Department of Orthopaedic Oncology, The People's Hospital of Liaoning Province, China Medical University People's Hospital, Shenyang, People's Republic of China.
Dose Response. 2020 Apr 23;18(2):1559325820920525. doi: 10.1177/1559325820920525. eCollection 2020 Apr-Jun.
Chondrosarcoma is the second most common bone malignancy in adults, and it is often resistant to traditional chemotherapy and radiation therapy. Permanent implantation of iodine-125 (I) seeds has been explored for the treatment of many types of cancer. In this study, the aim was to investigate the proliferative and microRNA (miRNA) effects of I seeds irradiation on human chondrosarcoma SW1353 cells. First, a new in vitro I seed irradiation model was established, and cell viability and miRNA microarray assays were performed before and after exposure to the I seeds. Cell proliferation was inhibited, and miRNA expression was substantially altered by irradiation exposure. The inhibition of cell proliferation was positively correlated with increased radiation doses, with cells showing the highest total radiation dose 7 days after irradiation. A total of 2549 miRNAs were detected in the SW1353 cells after exposure to 6 Gy of radiation, which included 189 differentially expressed miRNAs (98 upregulated and 91 downregulated). Four miRNAs were found to play important roles in the inhibition of cell proliferation after irradiation exposure, including miR-1224-5p, miR-492, miR-135b-5p, and miR-6839-5p. The target genes of the associated miRNAs mentioned were vascular endothelial growth factor A (), C-X-C motif chemokine 12 (), mitogen-activated protein kinase kinase kinase kinase 3 (), and apoptosis facilitator Bcl-2-like protein 14 (). Hence, the mitogen-activated protein kinase signaling pathway may be involved in how chondrosarcoma cells respond to I seed irradiation.
软骨肉瘤是成人中第二常见的骨恶性肿瘤,并且它通常对传统化疗和放射治疗具有抗性。碘-125(I)种子的永久植入已被探索用于治疗多种类型的癌症。在本研究中,目的是研究I种子照射对人软骨肉瘤SW1353细胞的增殖和微小RNA(miRNA)的影响。首先,建立了一种新的体外I种子照射模型,并在暴露于I种子之前和之后进行细胞活力和miRNA微阵列分析。照射暴露抑制了细胞增殖,并且miRNA表达发生了显著改变。细胞增殖的抑制与辐射剂量增加呈正相关,细胞在照射后7天显示出最高的总辐射剂量。在暴露于6 Gy辐射后,在SW13�3细胞中总共检测到2549个miRNA,其中包括189个差异表达的miRNA(98个上调和91个下调)。发现四个miRNA在照射暴露后对细胞增殖的抑制中起重要作用,包括miR-1224-5p、miR-492、miR-135b-5p和miR-6839-5p。上述相关miRNA的靶基因是血管内皮生长因子A、C-X-C基序趋化因子12、丝裂原活化蛋白激酶激酶激酶激酶3和凋亡促进因子Bcl-2样蛋白14。因此,丝裂原活化蛋白激酶信号通路可能参与软骨肉瘤细胞对I种子照射的反应方式。