Song Weiwei, Zhao Hengyu, Cui Zhongqi, Ma Xiaoyu, Zhang Wenwen, Wang Di, Liu Anqi, Yuan Lijie
Department of Pharmacology, Harbin Medical University, Harbin, People's Republic of China.
Daqing Oilfield General Hospital, Daqing, People's Republic of China.
Tumour Biol. 2016 Nov;37(11):15229-15240. doi: 10.1007/s13277-016-5404-4. Epub 2016 Sep 29.
Glioblastoma multiforme (GBM) is an aggressive tumor of the central nervous system characterized by high rates of recurrence, morbidity, and mortality. This study investigated the antitumor effects of an apoptin-derived peptide (ADP) on glioma cells and explored the underlying mechanisms. The U251, U87, and C6 glioma cell lines were used in the present study, and the expression of p-Akt, Akt, and MMP-9 was determined through Western blotting, quantitative real-time PCR, and hematoxylin and eosin (HE) staining. Tumor growth was evaluated by magnetic resonance imaging, and cell viability was assessed through an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide MTT assay. Glioma cell metastasis was evaluated using transwell migration, invasion, and scratch-wound assays. An ADP was designed and synthesized based on the results of a domain-based analysis of the structure of apoptin. The ADP inhibited glioma cell viability, invasion and migration, and treatment with the synthesized ADP led to downregulation of p-Akt and MMP-9 and inhibited MMP-9 translation. The ADP also inhibited glioma invasion and migration in vivo, and HE staining showed decreases in the satellite-like invasion of cell masses and apoptotic cell populations after treatment with the ADP. Our findings demonstrate that treatment with an ADP can suppress glioma cell migration and invasion via the PI3K/Akt/MMP-9 signaling pathway and provide a new platform for the development of drugs for treating glioma.
多形性胶质母细胞瘤（GBM）是一种侵袭性中枢神经系统肿瘤，其特点是复发率、发病率和死亡率高。本研究调查了一种凋亡素衍生肽（ADP）对胶质瘤细胞的抗肿瘤作用，并探讨了其潜在机制。本研究使用了U251、U87和C6胶质瘤细胞系，通过蛋白质免疫印迹法、定量实时聚合酶链反应和苏木精-伊红（HE）染色来测定p-Akt、Akt和基质金属蛋白酶-9（MMP-9）的表达。通过磁共振成像评估肿瘤生长情况，并通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐（MTT）法评估细胞活力。使用Transwell迁移、侵袭和划痕试验评估胶质瘤细胞转移情况。基于对凋亡素结构的结构域分析结果设计并合成了一种ADP。该ADP抑制了胶质瘤细胞的活力、侵袭和迁移，合成的ADP处理导致p-Akt和MMP-9下调，并抑制了MMP-9的翻译。ADP在体内也抑制了胶质瘤的侵袭和迁移，HE染色显示ADP处理后细胞团块的卫星样侵袭和凋亡细胞群体减少。我们的研究结果表明，ADP治疗可通过PI3K/Akt/MMP-9信号通路抑制胶质瘤细胞的迁移和侵袭，并为开发治疗胶质瘤的药物提供了一个新平台。
