Çıtışlı Veli, Dodurga Yavuz, Eroğlu Canan, Seçme Mücahit, Avcı Çığır Biray, Şatıroğlu-Tufan N Lale
Department of Neurosurgery, Pamukkale University School of Medicine, Denizli, Turkey.
Department of Medical Biology, Pamukkale University School of Medicine, Denizli, Turkey.
Tumour Biol. 2015 Sep;36(9):6765-72. doi: 10.1007/s13277-015-3373-7. Epub 2015 Apr 3.
Temozolomide (TMZ) is an alkylating drug used usually in glioma treatment by inducing the apoptosis in glioma cell. The aim of the study is to investigate the anticancer mechanism of TMZ in SH-SY5Y human neuroblastoma cell line. Cytotoxic effects of TMZ were determined by using XTT assay. IC50 doses in the SH-SY5Y were detected as 5 mM. Expression profiles of novel genes URG4/URGCP, CCND1, CCND2, CDK4, and BCL2 were determined by real-time PCR. The apoptotic effects of TMZ were evaluated with TUNEL method. Furthermore, effects of TMZ on colony formation and invasion were investigated in this study. It was observed that TMZ in SH-SY5Y cell line caused a significant decrease in the gene expressions of URG4/URGCP, CCND1, CCND2, CDK4, and BCL2. According to TUNEL assay results, TMZ markedly induced apoptosis in SH-SY5Y cell line. It was found that TMZ in SH-SY5Y cell line suppressed invasion and colony formation using matrigel invasion chamber and colony formation assay, respectively. To conclude, it is thought that TMZ demonstrates anticarcinogenesis activity by affecting cell cycle arrest, apoptosis, invasion, and colony formation on SH-SY5Y cells. TMZ may be an effective agent for treatment of neuroblastoma as a single or in combination with other drugs.
替莫唑胺（TMZ）是一种烷化剂药物，通常用于治疗神经胶质瘤，可诱导神经胶质瘤细胞凋亡。本研究旨在探讨TMZ对人神经母细胞瘤SH-SY5Y细胞系的抗癌机制。采用XTT法测定TMZ的细胞毒性作用。检测到TMZ在SH-SY5Y细胞系中的半数抑制浓度（IC50）为5 mM。通过实时PCR测定新基因URG4/URGCP、细胞周期蛋白D1（CCND1）、细胞周期蛋白D2（CCND2）、细胞周期蛋白依赖性激酶4（CDK4）和B细胞淋巴瘤-2（BCL2）的表达谱。采用TUNEL法评估TMZ的凋亡作用。此外，本研究还探讨了TMZ对集落形成和侵袭的影响。观察到TMZ可使SH-SY5Y细胞系中URG4/URGCP、CCND1、CCND2、CDK4和BCL2的基因表达显著降低。根据TUNEL检测结果，TMZ可显著诱导SH-SY5Y细胞系凋亡。分别使用基质胶侵袭小室和集落形成试验发现，TMZ可抑制SH-SY5Y细胞系的侵袭和集落形成。综上所述，认为TMZ通过影响SH-SY5Y细胞的细胞周期阻滞、凋亡、侵袭和集落形成发挥抗癌作用。TMZ作为单一药物或与其他药物联合使用可能是治疗神经母细胞瘤的有效药物。
