Atorvastatin and celecoxib inhibit prostate PC-3 tumors in immunodeficient mice.
OBJECTIVE
To investigate the effects and mechanisms of atorvastatin and celecoxib administered individually or in combination on human prostate cancer PC-3 cells cultured in vitro or grown as xenograft tumors in immunodeficient mice.


METHODS
Human prostate cancer PC-3 cells in culture were treated with atorvastatin and celecoxib alone or in combination. Severe combined immunodeficient (SCID) mice were injected s.c. with PC-3 cells. The mice received daily i.p injections starting 2 days before tumor cell inoculation and continuing during the course of treatment with atorvastatin (10 microg/g body weight/d), celecoxib (10 microg/g/d), a combination of atorvastatin (10 microg/g/d) and celecoxib (10 microg/g/d), or a combination of atorvastatin (5 microg/g/d) and celecoxib (5 microg/g/d).


RESULTS
Atorvastatin in combination with celecoxib had stronger effects on growth inhibition and apoptosis of PC-3 cells than either agent used individually. Atorvastatin and celecoxib in combination also had a stronger inhibitory effect on activation of nuclear factor-kappaB and extracellular signal-regulated kinase 1/2 in PC-3 cells than either agent alone. Treatment of SCID mice with combinations of atorvastatin and celecoxib more effectively inhibited the formation and growth of PC-3 tumors in the mice than either agent administered alone.


CONCLUSIONS
A combination of atorvastatin and celecoxib had a more potent inhibitory effect on the growth of PC-3 cells cultured in vitro or grown in SCID mice than either agent alone. A combination of atorvastatin and celecoxib may be an effective strategy for the prevention of prostate cancer.
Zheng
Xi
X
Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
Cui
Xiao-Xing
XX
Avila
Gina E
GE
Huang
Mou-Tuan
MT
Liu
Yue
Y
Patel
Jagruti
J
Kong
Ah Ng Tony
AN
Paulino
Raphael
R
Shih
Weichung Joe
WJ
Lin
Yong
Y
Rabson
Arnold B
AB
Reddy
Bandaru S
BS
Conney
Allan H
AH
D000818:Animals; D017209:Apoptosis; D000069059:Atorvastatin; D000068579:Celecoxib; D049109:Cell Proliferation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D016513:Mice, SCID; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D011720:Pyrazoles / Q000008:administration & dosage / Q000627:therapeutic use*; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D013449:Sulfonamides / Q000008:administration & dosage / Q000627:therapeutic use*; D023041:Xenograft Model Antitumor Assays
D016861:Cyclooxygenase Inhibitors; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011720:Pyrazoles; D011758:Pyrroles; D013449:Sulfonamides; D000069059:Atorvastatin; D000068579:Celecoxib