The Potential of Tetrandrine Against Gliomas
The Potential of Tetrandrine Against Gliomas
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DOI：
10.2174/187152010793498609
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发表时间：
2010-09-01
影响因子：
2.8
通讯作者：
Tseng, Sheng-Hong
中科院分区：
文献类型：
--
作者：
Chen, Yun;Tseng, Sheng-Hong
恶性胶质瘤患者预后较差，多数患者经过手术、放疗、化疗等多种治疗后肿瘤局部复发。因此，必须开发更好的治疗方法来治疗这些恶性脑肿瘤。粉防己碱是一种双苄基异喹啉生物碱，对某些癌症具有抗肿瘤作用。粉防己碱影响细胞周期、活性氧的产生、丝裂原激活的蛋白激酶活性，并逆转多种癌细胞的多药耐药。由于粉防己碱是一种低分子量的高脂溶性疏水分子，它可能穿过血脑屏障；因此，它可以用于治疗胶质瘤。粉防己碱抑制大电导钙活化钾（BK）通道，BK通道的表达与胶质瘤恶性程度呈正相关。此外，粉防己碱还发挥细胞毒性作用，通过消除辐射诱导的细胞周期扰动，诱导胶质瘤细胞凋亡和放射致敏。对胶质瘤有抗血管生成作用，对皮下胶质瘤和脑内胶质瘤有抗肿瘤作用。粉防己碱是一种放射增敏剂，也是一种多药耐药逆转剂。粉防己碱可能与放疗或其他化疗药物联合治疗胶质瘤。尽管如此，在任何临床应用之前，确定粉防己碱在恶性胶质瘤患者中的安全性和有效性之间的平衡是很重要的。
Patients with malignant gliomas have poor prognoses, and the majority of the patients have local tumor recurrence after various treatments including surgery, radiotherapy, and chemotherapy. Thus it is mandatory to develop better therapies for treatment of these malignant brain tumors. Tetrandrine, a bisbenzylisoquinoline alkaloid, has antitumor effects against some cancers. Tetrandrine affects the cell cycle, production of reactive oxygen species, mitogen-activated protein kinase activity, and reverses multidrug resistance in various cancer cells. Since tetrandrine is a highly lipid-soluble and hydrophobic molecule with a low molecular weight, it may cross the blood brain barrier; thus, it could be used for the treatment of gliomas. Tetrandrine inhibits the large-conductance, calcium-activated potassium (BK) channels and the expression of BK channel has a positive correlation with tumor malignancy grade in human gliomas. Furthermore, tetrandrine also exerts cytotoxic effects, and induces apoptosis and radiosensitization in glioma cells by elimination of radiation-induced cell cycle perturbation. It also has anti-angiogenesis effects in gliomas, and exerts an antitumor effect on subcutaneous and intracerebral gliomas. Tetrandrine is a radiosensitizer and also a multidrug resistance reversing agent. Tetrandrine can probably be combined with radiotherapy or other chemotherapeutic agents to treat gliomas. Nonetheless, it is important to determine the balance between the safety and efficacy of tetrandrine in patients with malignant gliomas before any clinical application.