Abstract
Cholangiocarcinoma (CCA) is a malignant tumor that arises from the epithelial cells of the bile duct and is notorious for its poor prognosis. The clinical outcome remains disappointing and thus more effective therapeutic options are urgently required. Cordycepin, a traditional Chinese medicine, provides multiple pharmacological strategies in anti-tumors, but its mechanisms have not been fully elucidated. In this study, we reported that cordycepin inhibited the viability of CCA cells and induced apoptosis via ERK1/2 deactivation. Moreover, cordycepin significantly reduced the angiogenetic capabilities of CCA in vitro. We also found that cordycepin inhibited DEK expression, an oncogenic protein that is overexpressed in various gastrointestinal tumors. DEK silencing inhibited CCA cell viability and angiogenesis, but not apoptosis induction. Furthermore, cordycepin significantly inhibited tumor growth in a xenograft model by downregulating the expression of DEK and p-ERK1/2. Taken together, we demonstrated that cordycepin inhibited CCA cell proliferation and angiogenesis with a DEK interaction via downregulation in ERK signaling. These data indicate that cordycepin may be a novel agent to improve CCA clinical treatment and prognosis.
SIGNIFICANCE STATEMENT Cordycepin provides multiple strategies in anti-tumors, but its mechanisms are not fully elucidated, especially on CCA. We reported that cordycepin inhibited the viability of CCA cells and induced apoptosis via ERK1/2 deactivation and DEK inhibition, reduced the angiogenetic capabilities of CCA both in vivo and in vitro.
- The American Society for Pharmacology and Experimental Therapeutics