Zhou Xiang, Zhao Xinli, Li Xiangsheng, Ping Guanfang, Pei Sujuan, Chen Ming, Wang Zhongwei, Zhou Wenke, Jin Baozhe
a Department of Neurosurgery , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China.
b Department of Pharmacy , First Affiliated Hospital of Xinxiang Medical College , Weihui , Henan , P. R. China.
J Chemother. 2016;28(1):44-9. doi: 10.1179/1973947815Y.0000000026.
Growth factor signalling pathways transduce extra-cellular physiological cues to guide cells to maintain critical cellular functions, including cell proliferation, survival and metabolism. Dysregulation of certain growth factor signalling pathways has been shown as a major route to promote tumourigenesis. Glioma is a type of aggressive malignant tumour with no effective systematic therapy so far. Overexpression or hyperactivation of IGF-1R has been observed to be tightly associated with glioma progression and poor prognosis. Here, we examined the biological effects of a specific IGF-1R inhibitor, PQ401, on suppressing U87MG glioma cell growth and migration. Specifically, we observed that PQ401 not only induced cellular apoptosis in U87MG cells and subsequently reduced cell viability and proliferation but also attenuated cell mobility in vitro. More importantly, through a mouse xenograft model, we observed that administration of PQ401 on mice led to suppression of glioma tumour growth in vivo. In summary, our study suggests that PQ401 may serve as a promising leading drug for treating glioma patients with elevated IGF-1R signalling.
生长因子信号通路转导细胞外生理信号，以引导细胞维持关键的细胞功能，包括细胞增殖、存活和代谢。某些生长因子信号通路的失调已被证明是促进肿瘤发生的主要途径。胶质瘤是一种侵袭性恶性肿瘤，目前尚无有效的系统治疗方法。已观察到IGF-1R的过表达或过度激活与胶质瘤进展和不良预后密切相关。在此，我们研究了一种特异性IGF-1R抑制剂PQ401对抑制U87MG胶质瘤细胞生长和迁移的生物学效应。具体而言，我们观察到PQ401不仅诱导U87MG细胞发生细胞凋亡，随后降低细胞活力和增殖，还在体外减弱细胞迁移能力。更重要的是，通过小鼠异种移植模型，我们观察到给小鼠施用PQ401可导致体内胶质瘤肿瘤生长受到抑制。总之，我们的研究表明，PQ401可能是治疗IGF-1R信号升高的胶质瘤患者的一种有前景的先导药物。
