脑胶质母细胞瘤是一种恶性程度极高的恶性肿瘤，由于肿瘤较强的侵润能力和化疗抵抗使该病患者5年生存率极低。为了提高患者的生存率，发现抑制肿瘤侵润能力以及抵抗肿瘤耐药的新型药物，可以为脑胶质母细胞瘤提供有效的治疗手段。前期研究我们发现尼克氨酸处理NIH3T3和HEK293细胞可以引起细胞内游离钙离子增高，引起细胞骨架解聚，迁移抑制。此外我们证实尼克氨酸对侵袭性很强的脑胶质母细胞瘤无论在体内还是在体外都有抑制其迁移的生物学活性，而且这种活性是通过促进脑胶质母细胞瘤细胞中Snail1蛋白降解来实现的。之后的研究中我们发现高浓度的尼克氨酸（14.0mM）能诱导脑胶质母细胞瘤凋亡。所以我们提出假设：高浓度尼克氨酸（14.0mM）诱导脑胶质母细胞瘤凋亡是通过调控细胞内钙和促进Snail1蛋白降解来实现的。我们本研究旨在进一步揭示尼克氨酸诱导脑胶质母细胞瘤凋亡的分子机制。

Glioblastoma multiforme (GBM) is a formidable disease that commonly leads to death, mainly due to the invasion and chemotherapy-resistance of tumor cells. Therefore, identification of de-novo chemical targets on the invasion and chemotherapy-resistance of tumor cells may provide an effective therapy for malignant glioma. Previously, we reported NA mobilizes and re-compartmentalizes the calcium into cytosol. Levitation of cytosolic calcium eventually leads to disassemble of cytoskeleton in NIH3T3 and HEK293 cells. Moreover, we recently demonstrated that nicotinic acid (NA), an essential vitamin, inhibits glioma cell invasion in vitro and in vivo mainly through facilitating the ubiquitination and degradation of Snail1. Upon the discoveries, we further find that higher concentration of NA (14.0 mM) is able to induce apoptosis of gliomablastoma cells. We therefore propose that higher concentration of NA (14.0 mM) induces apoptosis of gliomablastoma cells through both regulation of cytosolic calcium and stability of snail1 protein. This proposal is devoted to characterize the mechanism underlying NA induced apoptosis in GBM.