Published online Jul 14, 2019. doi: 10.3748/wjg.v25.i26.3380
Peer-review started: April 12, 2019
First decision: May 9, 2019
Revised: May 18, 2019
Accepted: May 31, 2019
Article in press: June 1, 2019
Published online: July 14, 2019
Bile duct cancer is characterized by fast metastasis and invasion and has been thought of as aggressive cancer due to the lack of effective diagnosis at an early stage. The 5-year survival rate of bile duct cancer has not substantially improved in clinical practice. In addition, it is reported that 5-fluorouracil (5-Fu) has been widely applied in treatments for various cancers, achieving a great therapeutic effect. Furthermore, raddeanin A (RA) plays essential proapoptotic roles in various types of tumor cells.
Exploring and developing effective diagnostic ways and therapies for bile duct cancer is greatly urgent for both basic science and clinical management.
The objective of this study was to determine the effects of RA on bile duct cancer cells and the underlying mechanisms.
In this study, RA at different concentrations was administered to four cholangiocarcinoma cell lines (RBE, LIPF155C, LIPF178C, and LICCF). Cell viability, Wound-healing migration, Transwell invasion, and Hoechst staining assays were performed to evaluate cell activities. Western blot analysis was performed to the apoptosis-related pathway.
RA inhibited cell viability in a dose-dependent pattern in the four cell lines. In RBE and LIPF155C cell lines, the migration and colony formation abilities were impaired by RA. Also, RA sensitized cell lines to 5-Fu treatment, promoting the effects of 5-Fu in cholangiocarcinoma cell lines. The role of RA was associated with reduced Wee1 expression. Furthermore, the combinational effect of RA and 5-Fu led to the inhibition of cyclooxygenase-2, B cell lymphoma 2, and Wee1 as well as the elevation of Bax, cyclin D1, and cyclin E.
RA administration could effectively regulate apoptosis and cell functions in cholangiocarcinoma cell lines in a Wee1-dependent pattern and promote the effect of 5-Fu in bile duct cancer. Collectively, RA is a promising treatment for bile duct cancer.
This study was aimed to provide clues to the application of RA for the therapy of bile duct cancer.