Harmine inhibits the proliferation and migration of glioblastoma cells via the FAK/AKT pathway

去氢骆驼蓬碱 蛋白激酶B 体内 细胞生长 癌症研究 PI3K/AKT/mTOR通路 化学 癌变 免疫印迹 分子生物学 信号转导 生物 药理学 生物化学 基因 生物技术
作者
Yuanchang Zhu,Yunxia Lv,Chen-Yi Guo,Zhimin Xiao,Qunguang Jiang,H B Kuang,Wenhua Zhang,Ping Hu
出处
期刊:Life Sciences [Elsevier]
卷期号:270: 119112-119112 被引量:16
标识
DOI:10.1016/j.lfs.2021.119112
摘要

Glioblastoma is one of the most invasive tumors of the central nervous system, and has a high degree of malignancy and poor prognosis. Harmine, an active ingredient extracted from perennial herbs, has been reported to have obvious antitumor effects on various tumors. However, the effects of harmine on glioblastoma growth remain unknown. We here explored the effects of harmine on glioblastoma and its underlying molecular mechanisms related to tumorigenesis. CCK-8 and immunofluorescent assay were performed to measure anti-proliferative effect of harmine on U251-MG and U373-MG cells. Wound healing assay was performed to measure the effects of harmine on cell migration. qRT-PCR and western blot were performed to detect the protein/gene expression. BALB/c nude mice bearing U251-MG xenografts was used to measure the effects of harmine on the growth of glioblastoma in vivo. Harmine treatment significantly suppressed the proliferation of U251-MG and U373-MG cells in a dose and time-dependent way. Mechanistically, harmine reduced the basal and EGF-enhanced the phosphorylation level of FAK and AKT. Moreover, harmine inhibited the cell viability of U251-MG and U373-MG cells by downregulating the phosphorylation of the FAK/AKT pathway. Besides, harmine significantly suppressed the migration of U251-MG cells by suppressing the expression of MMP2, MMP9 and VEGF. Subsequently, orthotopic xenograft models revealed that harmine treatment dramatically inhibited the growth of glioblastoma in vivo. In conclusion, these results suggest that harmine suppresses the proliferation and migration of U251-MG and U373-MG cells by inhibiting the FAK/AKT signaling pathway. Our findings elucidate harmine could be a promising drug for glioblastoma therapy.
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