Abstract
BackgroundIntrahepatic cholangiocarcinoma (ICC) is a malignancy with a hidden onset, high metastasis recurrence rate, and poor prognosis. Research on effective drugs for ICC is important for improving the prognosis of patients in the clinic. Brusatol is a quassinoid extracted from the seeds of Brucea sumatrana and has been shown to have the potential to inhibit tumor metastasis and proliferation. There has been no scientific research on the therapeutic effect of brusatol on ICC. Our study offers a novel strategy for the therapy of ICC. PurposeExplore effects of brusatol treatment on ICC and clarify the possible mechanism. Study DesignVarious cell functional experiments and basic experimental techniques were applied to ICC cell lines to explore the influences of brusatol on ICC cells; this conclusion was further verified in animal models. MethodsThe anti-cancer effects of the drug on the cell, protein, and RNA level were verified by cell functional experiments, WB blotting and transcriptome sequencing experiments, respectively. Finally, the experimental results were verified using subcutaneous tumor experiments in nude mice. ResultsThe consequences exhibited that the levels of epithelial markers of ICC cells increased after brusatol treatment, and the levels of interstitial indicators decreased, suppressing the epithelial-mesenchymal transition (EMT) process. Brusatol inhibited proliferation, induced apoptosis, and suppressed the migration and invasion abilities of Hucc-T1 and RBE oncocytes via activating PI3K/Akt pathway. It also suppressed the growth of Hucc-T1 xenografts in nude mice. ConclusionBrusatol inhibits the proliferation and EMT process in ICC oncocytes by the PI3K/Akt pathway and promotes apoptosis in oncocytes.
Published Version
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