Leng Tian-Dong, Li Ming-Hua, Shen Jian-Feng, Liu Ming-Li, Li Xin-Bo, Sun Hua-Wei, Branigan Debbie, Zeng Zhao, Si Hong-Fang, Li Jun, Chen Jeff, Xiong Zhi-Gang
Neuroscience Institute, Morehouse School of Medicine, Atlanta, GA, USA.
CNS Neurosci Ther. 2015 Mar;21(3):252-61. doi: 10.1111/cns.12354. Epub 2014 Dec 1.
Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor with a dismal prognosis. Despite intensive study on tumor biology, the underlying mechanisms of the unlimited proliferation and progressive local invasion are still poorly understood, and no effective treatment has been developed for GBM patients.
We determine the role of TRPM7 channels in the growth, migration, and infiltration of malignant glioma cells.
Using a combination of RT-PCR, Western blot, and patch-clamp techniques, we demonstrated the expression of functional TRPM7 channels of A172 cells, a human glioma cell line, as well as in human glioma tissues. Furthermore, we evaluated the role of TRPM7 in growth, migration, and infiltration of A172 cells with MTT and transwell migration and invasion assays.
We showed the expression of functional TRPM7 channels in both A172 cells and human glioma tissues. Suppression of TRPM7 expression with TRPM7-siRNA dramatically reduced the proliferation, migration, and invasion of A172 cells. Pharmacological inhibition of TRPM7 channel with 2-aminoethoxydiphenyl borate (2-APB) showed a similar effect as TRPM7-siRNA.
We demonstrate that human glioma cells express functional TRPM7 channel and that activation of this channel plays an important role in the proliferation, migration, and invasion of malignant glioma cells. TRPM7 channel may represent a novel and promising target for therapeutic intervention of malignant glioma.
多形性胶质母细胞瘤(GBM)是最常见且侵袭性最强的原发性脑肿瘤,预后极差。尽管对肿瘤生物学进行了深入研究,但对其无限增殖和局部侵袭进展的潜在机制仍了解甚少,且尚未开发出针对GBM患者的有效治疗方法。
我们确定瞬时受体电位M型7通道(TRPM7通道)在恶性胶质瘤细胞生长、迁移和浸润中的作用。
我们运用逆转录聚合酶链反应(RT-PCR)、蛋白质免疫印迹法(Western blot)和膜片钳技术相结合的方法,证实了人胶质瘤细胞系A172细胞以及人胶质瘤组织中功能性TRPM7通道的表达。此外,我们通过MTT法以及Transwell迁移和侵袭实验评估了TRPM7在A172细胞生长、迁移和浸润中的作用。
我们发现A172细胞和人胶质瘤组织中均有功能性TRPM7通道的表达。用TRPM7小干扰RNA(TRPM7-siRNA)抑制TRPM7表达可显著降低A172细胞的增殖、迁移和侵袭能力。用2-氨基乙氧基二苯硼酸(2-APB)对TRPM7通道进行药理学抑制显示出与TRPM7-siRNA类似的效果。
我们证明人胶质瘤细胞表达功能性TRPM7通道,且该通道的激活在恶性胶质瘤细胞的增殖、迁移和侵袭中起重要作用。TRPM7通道可能是恶性胶质瘤治疗干预的一个新的有前景的靶点。