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Atorvastatin and Celecoxib Inhibit Prostate PC-3 Tumors in Immunodeficient Mice

Authors' Affiliations: ¹ Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology and ² Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, and ³ Center for Advanced Biotechnology and Medicine and the University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, Piscataway, New Jersey; and ⁴ Department of Biostatistics, School of Public Health, University of Medicine and Dentistry of New Jersey, and ⁵ Cancer Institute of New Jersey, New Brunswick, New Jersey

Requests for reprints: Allan H. Conney, Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical Biology, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854. Phone: 732-445-4940; Fax: 732-445-0687; E-mail: aconney{at}rci.rutgers.edu.

Purpose: 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.

Experimental Design: 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 µg/g body weight/d), celecoxib (10 µg/g/d), a combination of atorvastatin (10 µg/g/d) and celecoxib (10 µg/g/d), or a combination of atorvastatin (5 µg/g/d) and celecoxib (5 µg/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-B 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.