Suppressive control of glioma invasions via inhibition of sodium ion/proton exchanger 1

对利用在体外表现出有希望的潜力的5-（N-乙基-N-异丙基）-阿米洛利（EIPA）开发新型抗肿瘤侵袭药物进行了临床前评价，旨在开发一种新的针对胶质瘤的有效治疗方法，其治疗方法长期以来一直没有改进。在探索EIPA的作用机制的过程中，发现了一种特征性的血管参与了胶质瘤细胞的侵袭，提示TGF β 1的活化过程可能参与了这一步骤。此外，从EIPA钠离子/质子交换剂1（NHE 1）的靶点对头颈部鳞状细胞癌细胞（SCC）淋巴结转移的贡献的观察，证实了将EIPA视为抗肿瘤侵袭药物的有效性。与非转移性亲本细胞系相比，SCC的高转移性亚系细胞获得了NHE 1的增强表达，并且NHE 1的敲低降低了转移。

Preclinical evaluations for the development of a novel anti-tumor invasion medicine by utilization of 5-(N-ethyl-N-isopropyl)-amiloride (EIPA) which had exhibited promising potential in vitro were performed, aiming at developing a novel powerful therapy against gliomas of which treatment has long been unimproved. On the way of the explorations of modes of action of EIPA, a characteristic blood vessel was found to contribute to the glioma cell invasions, and an implication that activation process of TGFbeta1 may participate in this step was obtained. Furthermore, the validity to consider EIPA as an anti-tumor invasion medicine was confirmed from the observation of contributions of the target of EIPA sodium ion/proton exchanger1 (NHE1) on lymph node metastasis of head and neck squamous cell carcinoma cells (SCC). Highly metastatic subline-cell of a SCC acquired enhanced expression of NHE1 compared with the non-metastatic parental cell line, and knockdown of NHE1 reduced the metastasis.