褪黑素对胶质瘤细胞迁移和侵袭的影响及其机制研究

Glioma，which takes about 50% of all primary tumors in adult brain，is the most common primary brain tumor. High proliferation, migration and invasion are the main characteristics that responding for incurable of glioma. Therefore, the control of metastasis and invasion represents an important therapeutic target in the treatment of glioma. However, the present therapy strategies are limited in view of neural toxicity, hematologic toxicity, or difficulty in crossing the blood-brain barrier (BBB) of many drugs. Thus, development of new therapeutic strategies that are effective in inhibition of tumor progression and less toxicity as well as readily crossing the BBB is desirable. Melatonin is an indolamine that is synthesized by the pineal gland and the suprachiasmatic nucleus as well as peripheral tissues. Recent interest on melatonin has been focused on its potential antitumor effects in many types of tumors including prostate cancer.In glioma cells, millimolar concentration of melatonin can reduce growth and inhibit cell progression from G1 to S phase of the cell cycle. However, the effect of melatonin on migration and invasion of glioma has been remained to be explored and elucidated. Glioma is a kind of tumor which derived from the neural epithelium. Epithelial-mesenchymal transition (EMT) is a process featured in cell migration and reduced cellular adhesion. In general, the process of EMT is the inhibition of the epithelial marker Epithelial cadherin (E-cadherin) and excitation of the mesenchymal marker Neural cadherin (N-cadherin). In the present study, we intend to subject the role of EMT plays in the effect of melatonin in the migration and invasion of glioma cells.

人脑胶质瘤是中枢神经系统最常见的原发肿瘤，约占中枢神经系统原发性肿瘤的50%。胶质瘤病人的预后差、死亡率高，现有的治疗方法对胶质瘤的控制效果一般，究其原因，主要是其具有很强的侵袭能力。因此，有效控制肿瘤细胞的侵袭才能有效地治疗胶质瘤。褪黑素是由松果体视交叉上核及周围组织合成分泌的一种神经内分泌激素。最近研究发现褪黑素具有抗肿瘤的作用，能够抑制包括前列腺癌在内的等多种肿瘤的生长。我们的前期研究结果显示一定浓度的褪黑素能够抑制胶质瘤细胞的迁移和侵袭，其作用可能与其对肿瘤细胞氧化应激反应的抑制 有关,但其作用机制仍不明确。褪黑素可以上调肿瘤细胞上皮型钙粘蛋白而抑制神经型钙粘蛋白的表达,提示其可能影响细胞上皮-间质转化。本课题拟就此问题展开研究，以揭示褪黑素对胶质瘤细胞迁移和侵袭的影响及作用机制，为褪黑素的临床应用提供实验依据。