Department of Biophysics, School of Physics Science, Nankai University, Tianjin 300071, China.
Biochem Biophys Res Commun. 2013 Aug 23;438(2):312-7. doi: 10.1016/j.bbrc.2013.07.067. Epub 2013 Jul 24.
In contrast to the voltage-gated K(+) channels, the voltage-gated proton channel Hv1 contains a voltage-sensor domain but lacks a pore domain. Here, we showed that Hv1 is expressed in the highly metastatic glioma cell SHG-44, but lowly in the poorly metastatic glioma cell U-251. Inhibition of Hv1 activity by 140μM zinc chloride induces apoptosis in the human highly metastatic glioma cells. Zn(2+) ions markedly inhibit proton secretion, and reduce the gelatinase activity in the highly metastatic glioma cells. In vivo, the glioma tumor sizes of the implantation of the SHG-44 xenografts in nude mice that were injected zinc chloride solution, were dramatically smaller than that in the controlled groups. The results demonstrated that the inhibition of Hv1 activity via Zn(2+) ions can effectively retard the cancer growth and suppress the cancer metastasis by the decrease of proton extrusion and the down-regulation of gelatinase activity. Our results suggest that Zn(2+) ions may be used as a potential anti-glioma drug for glioma therapy.
与电压门控钾 (K+) 通道相反，电压门控质子通道 Hv1 包含一个电压传感器结构域，但缺乏一个孔结构域。在这里，我们表明 Hv1 在高度转移性神经胶质瘤细胞 SHG-44 中表达，但在低度转移性神经胶质瘤细胞 U-251 中表达水平较低。用 140μM 氯化锌抑制 Hv1 活性会诱导人高度转移性神经胶质瘤细胞凋亡。Zn(2+) 离子显著抑制质子分泌，并降低高度转移性神经胶质瘤细胞中的明胶酶活性。在体内，注射氯化锌溶液的 SHG-44 异种移植裸鼠的神经胶质瘤肿瘤大小明显小于对照组。结果表明，通过 Zn(2+) 离子抑制 Hv1 活性可以通过减少质子外排和下调明胶酶活性有效抑制肿瘤生长和抑制肿瘤转移。我们的结果表明，Zn(2+) 离子可能被用作神经胶质瘤治疗的一种潜在的抗神经胶质瘤药物。
