Abstract 2100: Inhibition of androgen-independent growth of LNCaP xenograft tumors in immunodeficient mice by a combination of atorvastatin (Lipitor) and celecoxib (Celebrex)

Abstract

Abstract Epidemiological studies indicate that statins and non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the risk of prostate cancer. In the present study, we assessed the effects of Lipitor and Celebrex alone or in combination on androgen-independent growth of human prostate cancer LNCaP cells cultured in vitro or grown as xenograft tumors in immunodeficient mice. In the in vitro studies, LNCaP cells were cultured in medium supplemented with charcoal-stripped fetal bovine serum to mimic androgen-deprivation treatment. We found that treatment of LNCaP cells cultured in androgen-depleted medium with Lipitor or Celebrex alone resulted in growth inhibition and apoptosis. A combination of Lipitor and Celebrex had more potent effects on growth inhibition and apoptosis than either agent alone. In animal studies, severe combined immunodeficient (SCID) mice were injected subcutaneously with LNCaP cells in Matrigel. After 4-6 weeks, mice with LNCaP tumors (about 0.6 cm wide and 0.6 cm long) were surgically castrated and received daily i.p injections with vehicle, Lipitor (10 μg/g body weight/day), Celebrex (10 μg/g/day) or a combination of Lipitor (5 μg/g/day) and Celebrex (5 μg/g/day) for 42 days. In the vehicle control group, LNCaP tumors regressed initially in response to castration and then re-grew in 2 weeks after castration to develop androgen-independent tumors. Treatment of the mice with Lipitor or Celebrex alone suppressed the re-growth of LNCaP tumors after castration. A combination of low doses of Lipitor and Celebrex had a more potent effect for inhibiting the androgen-independent growth of LNCaP tumors than a higher dose of either agent alone. The results from our study indicate that a combination of Lipitor and Celebrex may be an effective strategy for the prevention of prostate cancer progression from androgen-dependence to an androgen-independent stage.