Triptolide inhibits intrahepatic cholangiocarcinoma growth by suppressing glycolysis via the AKT/mTOR pathway.

Background: High levels of glycolysis supply large quantities of energy and biological macromolecular raw materials for cell proliferation. Triptolide (TP) is a kind of epoxy diterpene lactone extracted from the roots, flowers, leaves, or grains of the Celastraceae plant, Tripterygium wilfordii. TP has multiple biological activities, including anti-inflammatory, immunologic suppression, and anti-cancer effects. Nevertheless, it is little known regarding its anti-intrahepatic cholangiocarcinoma (ICC) growth, and the mechanism still require exploration.

Purpose: This research explored the effect of TP on ICC growth and investigated whether TP inhibits glycolysis via the AKT/mTOR pathway.

Methods: Cell proliferation was analyzed by Cell Counting Kit-8 (CCK-8), clonogenic assay, and flow cytometry. The underlying molecular mechanism was identified by determining glucose consumption, ATP production, lactate production, hexokinase (HK) and pyruvate kinase (PK) activity, and Western blot analysis. A rapid ICC model of AKT/YapS127A oncogene coactivation in mice was used to clarify the effect of TP treatment on tumor growth and glycolysis.

Results: The results showed that TP treatment significantly inhibited ICC cell proliferation and glycolysis in a dose- and time-dependent manner(P < 0.05). Further analysis suggested that TP suppressed ICC cell glycolysis by targeting AKT/mTOR signaling. Additionally, we found that TP inhibits tumor growth and glycolysis in AKT/YapS127A mice(P < 0.05).

Conclusion: Taken together, we revealed that TP suppressed ICC growth by suppressing glycolysis via the AKT/mTOR pathway and may provide a potential therapeutic target for ICC treatment.