1. Academic Validation
  2. Harmine inhibits the proliferation and migration of glioblastoma cells via the FAK/AKT pathway

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

  • Life Sci. 2021 Apr 1;270:119112. doi: 10.1016/j.lfs.2021.119112.
Yu-Ge Zhu 1 Yun-Xia Lv 2 Chen-Yi Guo 3 Zhi-Min Xiao 3 Qun-Guang Jiang 4 Huang Kuang 1 Wen-Hua Zhang 3 Ping Hu 5
Affiliations

Affiliations

  • 1 Institute of Translational Medicine, Nanchang University, 1299 Xuefu Avenue, Nanchang, Jiangxi 330001, PR China.
  • 2 Department of Thyroid Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, PR China.
  • 3 Institute of Life Science, Nanchang University, 1299 Xuefu Avenue, Nanchang, Jiangxi 330031, PR China.
  • 4 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi, PR China.
  • 5 Institute of Translational Medicine, Nanchang University, 1299 Xuefu Avenue, Nanchang, Jiangxi 330001, PR China. Electronic address: canyhp@ncu.edu.cn.
Abstract

Aims: 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.

Materials and methods: 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.

Key findings: 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.

Significance: 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.

Keywords

FAK; Glioblastoma; Harmine; Migration; Proliferation.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-10459
    99.68%, FAK/Pyk2 Inhibitor