Effects of atorvastatin in combination with celecoxib and tipifarnib on proliferation and apoptosis in pancreatic cancer sphere-forming cells.
Eur J Pharmacol
; 893: 173840, 2021 Feb 15.
Article
in En
| MEDLINE
| ID: mdl-33359649
ABSTRACT
Cancer stem cell (CSC) plays an important role in pancreatic cancer pathogenesis and treatment failure. CSCs are characterized by their ability to form tumor spheres in serum-free medium and expression of CSC related markers. In the present study, we investigated the effect atorvastatin, celecoxib and tipifarnib in combination on proliferation and apoptosis in Panc-1 sphere-forming cells. The sphere-forming cells were isolated from Panc-1 cells by sphere-forming method. These sphere-forming cells showed CSC properties. The levels of CD44, CD133 and ALDH1A1 in the sphere-forming cells were increased. Moreover, Panc-1 sphere-forming cells were resistant to chemotherapeutic drug gemcitabine. Combined atorvastatin with celecoxib and tipifarnib synergistically decreased the sphere forming ability of Panc-1 cells and the drug combination also strongly inhibited cell proliferation and promoted apoptosis in the sphere-forming cells. The effects of the drug combination on the Panc-1 sphere-forming cells were associated with decreases in the levels of CD44, CD133 and ALDH1A1, and suppression of Akt and NF-κB activation. Results of the present study indicate that the combination of atorvastatin, celecoxib and tipifarnib may represent an effective approach for inhibiting pancreatic CSCs.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Pancreatic Neoplasms
/
Neoplastic Stem Cells
/
Antineoplastic Combined Chemotherapy Protocols
/
Apoptosis
/
Quinolones
/
Cell Proliferation
/
Celecoxib
/
Atorvastatin
Limits:
Humans
Language:
En
Journal:
Eur J Pharmacol
Year:
2021
Document type:
Article