Inhibition of EGFR-induced glucose metabolism sensitizes chondrosarcoma cells to cisplatin
Inhibition of EGFR-induced glucose metabolism sensitizes chondrosarcoma cells to cisplatin
复制标题
DOI：
10.1007/s13277-014-1902-4
复制
发表时间：
2014-07-01
期刊：
影响因子：
--
通讯作者：
Shi, Feng-jun
中科院分区：
文献类型：
--
作者：
Song, Yin-dong;Zhang, Ke-fei;Shi, Feng-jun
软骨肉瘤是一种恶性软骨形成肿瘤，对常规化疗和放疗有抵抗力。通过检索Oncomine这是一个癌症微阵列数据库和基于Web的数据挖掘平台，我们发现Glut1和LDHA在人类软骨肉瘤患者样本中上调。在这项研究中，我们报告了总表皮生长因子受体（EGFR）的表达和磷酸化EGFR高度激活的人软骨肉瘤细胞系。此外，EGFR的过度表达有助于顺铂耐药。EGFR通过上调糖酵解关键酶的表达促进软骨肉瘤细胞糖代谢。有趣的是，顺铂耐药软骨肉瘤细胞显示出上调的葡萄糖代谢和EGFR信号通路。最后，我们证明了EGFR抑制剂或厌氧糖酵解抑制剂与顺铂的组合通过诱导细胞凋亡和细胞周期阻滞对顺铂耐药软骨肉瘤细胞表现出协同抑制作用。我们的项目提出了一个新的功能，表皮生长因子受体在软骨肉瘤细胞的葡萄糖代谢的调节，并为软骨肉瘤患者的临床治疗策略的发展做出了贡献。
Chondrosarcomas are malignant cartilage-forming tumors which are resistant to conventional chemotherapy and radiotherapy. By searching in Oncomine which is a cancer microarray database and web-based data mining platform, we found Glut1 and LDHA were upregulated in human chondrosarcoma patient samples. In this study, we reported total epidermal growth factor receptor (EGFR) expression and phosphorylated EGFR were highly activated in human chondrosarcoma cell lines. In addition, overexpression of EGFR contributed to cisplatin resistance. EGFR promoted glucose metabolism of chondrosarcoma cells through the upregulation of glycolysis key enzymes. Interestingly, cisplatin-resistant chondrosarcoma cells showed upregulated glucose metabolism and EGFR signaling pathway. Finally, we demonstrated that the combination of either EGFR inhibitor or anaerobic glycolysis inhibitor with cisplatin showed synergistically inhibitory effects on cisplatin-resistant chondrosarcoma cells through the inducements of apoptosis and cell cycle arrest. Our project proposed a novel function of EGFR in the regulation of glucose metabolism in chondrosarcoma cells and contributed to the development of therapeutic strategies for the clinical treatment of chondrosarcoma patient.