Tetramethylpyrazine (TMP) protects cerebral neurocytes and inhibits glioma by down regulating chemokine receptor CXCR4 expression
Tetramethylpyrazine (TMP) protects cerebral neurocytes and inhibits glioma by down regulating chemokine receptor CXCR4 expression
复制标题
四甲基吡嗪（TMP）通过下调趋化因子受体CXCR4表达保护脑神经细胞并抑制胶质瘤
DOI：
10.1016/j.canlet.2013.03.015
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发表时间：
2013-08-19
期刊：
影响因子：
9.7
通讯作者：
Zhuang, Jing
中科院分区：
文献类型：
--
作者：
Chen, Zhao;Pan, Xueke;Zhuang, Jing
恶性胶质瘤患者的存活率仍然有限，迫切需要新的治疗策略。从中草药川芎中提取的川芎嗪(TMP)被认为主要是通过其神经保护作用而具有治疗胶质瘤的潜力。然而，TMP的抗肿瘤作用和神经保护作用的确切机制尚未阐明。因此，本研究旨在探讨TMP在肿瘤抑制和神经保护方面的分子靶点。原代培养的大脑神经细胞用100MU TMP处理14d。我们发现，与对照组相比，TMP可以有效地促进神经元存活。与对照组相比，TMP能有效抑制H_2O_2诱导的脑神经细胞[Ca~(2+)](I)升高和谷氨酸释放。此外，我们验证了先前的结果，TMP显著降低了C6胶质瘤细胞的迁移和增殖。采用神经胶质瘤-神经细胞共培养体系，进一步证实了TMP对胶质瘤细胞的抑制和对脑神经细胞的保护作用。更重要的是，我们的研究表明，在肿瘤发生和各种神经退行性疾病中起关键作用的趋化因子受体CXCR4在TMP处理的大脑神经细胞和C6胶质瘤细胞中的表达显著降低，无论是单独培养还是联合培养。与CXCR4拮抗剂AMD3100相比，TMP对脑胶质瘤的抑制和神经保护作用更强。共培养体系经100亩TMP处理后，培养液中谷氨酸浓度降低。因此，我们的研究结果表明，TMP介导的C6胶质瘤抑制和神经保护涉及到抑制CXCR4的表达。因此，这项研究为TMP在治疗恶性胶质瘤方面的治疗潜力提供了新的见解。(C)2013爱思唯尔爱尔兰有限公司。保留所有权利。
The survival in patients with malignant gliomas still remains limited and novel treatment strategies are urgently needed. Tetramethylpyrazine (TMP) extracted from the Chinese herb Chuanxiong, has been suggested to have a therapeutic potential towards glioma primarily through its neural protection activity. However, the exact mechanisms correlating TMP's antitumor function and neural protection have not been yet elucidated. Thus, this study aimed to investigate TMP's molecular target in tumor inhibition and neural protection. The primary cultured cerebral neurocytes were treated with 100 mu M TMP for 14 days in vitro. We found TMP can effectively promote neurons survival, compared to controls. TMP effectively inhibits H2O2-induced rise of [Ca2+](i) and glutamate releasing in cerebral neurocytes, compared to controls. In addition, we verify previous results that TMP significantly decreases the migration and proliferation of C6 glioma cells. Using glioma-neuronal co-culturing system, we further confirm TMP bioactivity in inhibition of glioma cells and protection of cerebral neurocytes. More importantly, our study demonstrates that the expression of chemokine receptor, CXCR4, which plays a key role in tumor development and various neurodegenerative diseases, is significantly decreased in both cerebral neurocytes and C6 glioma cells with TMP treatment, cultured alone or co-cultured. Compared with CXCR4 antagonist, AMD3100, TMP is more effective on glioma inhibition and neural protection. Glutamate concentration in medium of co-culturing system was lower after treatment with 100 mu M TMP. Therefore, our findings suggest that TMP-mediated suppression of C6 gliomas and neural protection involves inhibition of CXCR4 expression. Thus, this study provides new insights into TMP's therapeutic potential in the treatment of malignant gliomas. (C) 2013 Elsevier Ireland Ltd. All rights reserved.