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BACKGROUND & AIMS: Salicylate activates AMPK, inhibits mTORC1 signaling in some cancer cells, GBM cells have dysregulated RTK/mTOR signaling, which promotes cell survival, proliferation and tumor growth. Thus, the goal of this study was to investigate the effects of salicylate on proliferation, AMPK and RTK/mTOR signaling in human GBM cell lines. METHODS: MTT assay, colony formation assay, and flow cytometry were used to evaluate the effects of salicylate on proliferation in GBM cell lines. The effects of salicylate on AMPK and RTK/mTOR signaling in GBM cell lines were determined by the expression of PDGFR, phosphorylation of ACC, S6 and 4EBP1 via immunoblotting. Ubiquitin-like protein LC3 was used as the marker of autophagy and was examined in GBM cell lines by immunoblotting. RESULTS: Salicylate inhibited proliferation, induced apoptosis and S phase cycle arrest in GBM cell lines. Salicylate activated AMPK, down-regulated PDGFR, and reduced mTORC1 signaling by inhibiting mTORC1 substrates S6 and 4EBP1 in GBM cell lines. Salicylate also activated autophagy, which is a characterized response of the inhibition of mTORC1. CONCLUSIONS: Salicylate is a potential anti-GBM agent, and it may exert its anti-neoplasm activity by modulation of AMPK and PDGFR/mTORC1 signaling, which is pivotal for GBM progression. Our data will also serve as the basis for in vivo studies to investigate the effects of salicylate on GBM.????? |
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Keywords:Glioblastoma multiforme (GBM); Salicylate; RTK/mTOR signal; AMPK; Autophagy |
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