Novel Small Molecular Compound AE-848 Showed Potent Inhibitory Activity Against Human Hepatoblastoma Cells

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Abstract Purpose AE-848/33345007, is a novel small molecular compound that was independently synthesized by our laboratory. The aim of the current study was to investigate potential therapeutic effects of the small molecule compound AE-848 on human hepatoblastoma cells. Methods Human hepatoblastoma cell line HepG2 was cultured under different concentrations of AE-848. MTT assay was used to detect the inhibitory ability of AE-848 on the activity of this cell line, while flow cytometry was applied to quantify apoptosis. Western-blot technique was used to determine expression levels of signaling pathway-associated molecules. The antitumor in vivo activity of AE-848 against hepatoblastoma was evaluated using hepatoblastoma-bearing nude mice randomly divided into AE-848 (experimental) and saline (control) groups respectively. Changes in survival and tumor sizes were compared between these two groups. Results AE-848 significantly inhibited proliferation and induced apoptosis of HepG2 cells, and induced activation of PI3K/Akt/mTOR signaling pathways. More importantly, AE-848 administration significantly inhibited tumor growth and prolonged survival of hepatoblastoma-bearing mice. Conclusion AE-848 had a strong anti-hepatoblastoma activity both in vitro and in vivo , indicating the importance of developing AE-848 as a potential drug for hepatoblastoma treatment.

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