Osteosarcoma cell proliferation and survival requires mGluR5 receptor activity and is blocked by Riluzole.
Osteosarcoma cell proliferation and survival requires mGluR5 receptor activity and is blocked by Riluzole.
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DOI：
10.1371/journal.pone.0171256
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Mahajan SS
中科院分区：
文献类型：
--
作者：
Liao S;Ruiz Y;Gulzar H;Yelskaya Z;Ait Taouit L;Houssou M;Jaikaran T;Schvarts Y;Kozlitina K;Basu-Roy U;Mansukhani A;Mahajan SS
骨肉瘤是一种骨的恶性肿瘤，最常见于儿童和青少年。尽管现代医学取得了进步，但转移性骨肉瘤的低存活率在过去20年里并没有改善。在本研究中，我们研究了利鲁唑对人和小鼠转移性骨肉瘤细胞的影响。我们发现LM7细胞在培养液中分泌谷氨酸，mGluR5受体是LM7细胞增殖所必需的。利鲁唑可以抑制谷氨酸的释放，抑制LM7细胞的增殖，诱导细胞凋亡，阻止细胞迁移。MGluR5的特异性阻滞剂非诺班也出现了这种情况。我们还发现，利鲁唑改变了AKT/P70 S6激酶、ERK1/2和JNK1/2的磷酸化状态。因此，利鲁唑是一种有效的抑制骨肉瘤细胞增殖和存活的药物，对具有自分泌谷氨酸信号的骨肉瘤具有治疗潜力。
Osteosarcomas are malignant tumors of bone, most commonly seen in children and adolescents. Despite advances in modern medicine, the poor survival rate of metastatic osteosarcoma has not improved in two decades. In the present study we have investigated the effect of Riluzole on a human and mouse metastatic osteosarcoma cells. We show that LM7 cells secrete glutamate in the media and that mGluR5 receptors are required for the proliferation of LM7 cells. Riluzole, which is known to inhibit glutamate release, inhibits proliferation, induces apoptosis and prevents migration of LM7 cells. This is also seen with Fenobam, a specific blocker of mGluR5. We also show that Riluzole alters the phosphorylation status of AKT/P70 S6 kinase, ERK1/2 and JNK1/2. Thus Riluzole is an effective drug to inhibit proliferation and survival of osteosarcoma cells and has therapeutic potential for the treatment of osteosarcoma exhibiting autocrine glutamate signaling.