Isorhamnetin inhibits cholangiocarcinoma proliferation and metastasis via PI3K/AKT signaling pathway.

Abstract

Background: Cholangiocarcinoma (CCA), which is a malignant tumor originating from the epithelial cells of the bile ducts, has witnessed an increasing incidence year by year. Owing to the dearth of effective treatments, the prognosis for CCA is rather poor. Isorhamnetin is known to possess anti-tumor, anti-inflammatory and oxidative stress modulating effects; however, its role in CCA remains unclear.

Methods: Firstly, we screened the core targets and pathways of isorhamnetin for the treatment of CCA through a network pharmacology approach. Subsequently, we verified via molecular docking that the core targets could dock stably with isorhamnetin. Finally, we verified the inhibitory effect of isorhamnetin on the malignant biological behavior of CCA in vitro and in vivo experiments.

Results: Based on the network pharmacology analysis, we came to the conclusion that AKT1 might be a core target of isorhamnetin in the treatment of CCA. Molecular docking indicated that AKT1 was capable of binding stably to isorhamnetin. Subsequently, In vitro experiments demonstrated that isorhamnetin was able to suppress the proliferation and metastasis of CCA cells, and AKT1 played a pivotal role in this process. Mechanistically speaking, isorhamnetin exerts its inhibitory effect on tumor growth via the PI3K/AKT signaling pathway.

Conclusions: Our study demonstrated for the first time that isorhamnetin can inhibit the progression of CCA through PI3K/AKT, and that AKT1 may be a target of isorhamnetin for the treatment of CCA.