Epidemiologic studies indicate the use of either
statins or
aspirin have beneficial effects in
prostate cancer patients. The present study was undertaken to evaluate the effects and mechanisms of
atorvastatin and
aspirin alone or in combination in human
prostate cancer cells cultured in vitro and grown as xenograft
tumors in severe combined immune-deficient (SCID) mice. The growth and apoptosis in
prostate cancer cells were determined by the
trypan blue exclusion and
propidium iodide staining assays. Activation of the nuclear factor κB (NF-κB) was measured by
luciferase reporter assay, and the levels of phospho-signal transducer and activator of transcription (Stat)3 and phospho-
extracellular signal-regulated kinase (Erk)1/2 were determined by western blot analysis. Mice were injected subcutaneously with PC-3 cells in
Matrigel. After 4-6 weeks, mice with PC-3
tumors received i.p. injections of vehicle,
atorvastatin (5 mg/kg),
aspirin (80 mg/kg), or
atorvastatin (5 mg/kg) +
aspirin (80 mg/kg) three times a week for 30 days. Our results demonstrated the combination of
atorvastatin and
aspirin had more potent effects on growth inhibition and apoptosis stimulation in
prostate cancer cells than either drug alone. Mechanistic studies indicated the induction of apoptosis in PC-3 cells was associated with strong inhibition of NF-κB and decreases in the levels of phospho-Stat3 and phospho-Erk1/2. Results of the present study demonstrated a strong combined effect of
atorvastatin and
aspirin on inhibiting the growth of
prostate cancer cells in vitro and in vivo. The findings provide a strong rationale for clinical evaluation of the combination of
atorvastatin and
aspirin in patients with
prostate cancer.