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Statin/NSAID combo inhibits androgen-independent prostate cancer growth
Megan Rauscher
Last Updated: 2008-04-15 9:57:16 -0400 (Reuters Health)
NEW YORK (Reuters Health) - A combination of a low dose of atorvastatin (Lipitor) and a low dose of celecoxib (Celebrex) potently inhibits the androgen-independent growth of prostate cancer in an animal model, according to research reported Monday at the American Association of Cancer Research 2008 annual meeting in San Diego.
"Our results suggest a need for clinical trials to determine whether a combination of Lipitor and Celebrex will inhibit or prevent the transition of androgen-dependent prostate cancer, which is the easily treatable form of the tumor, to the more aggressive androgen-independent prostate cancer," Dr. Xi Zheng from Rutgers University, New Brunswick, New Jersey, told the conference.
In human prostate cancer cells cultured in androgen-depleted medium, treatment with Lipitor or Celebrex alone resulted in growth inhibition and apoptosis. "We found that the combination has a more potent effect of suppressing the cancer cell growth and for inducing cancer cell death than either drug used alone," Dr. Zheng reported.
In a follow up animal study, mice with androgen-dependent prostate cancer were deprived of androgen by surgical removal of the testes and randomly assigned to 10 micrograms per gram of body weight per day of Lipitor or the same dose of Celebrex, or to a combination of each drug at 5 mcg/g per day, or to no treatment.
According to Dr. Zheng, all mice experienced temporary tumor regression in the absence of androgen. As tumors became androgen-independent, untreated mice experienced substantial tumor regrowth, whereas treated mice were protected from the transition from androgen-dependent to androgen-independent status.
Administration of atorvastatin or celecoxib alone "delayed the time for the tumor to become androgen-independent and regrow," Dr. Zheng noted, "and the combination was more effective than the individual drugs alone."
"Administration of the two drugs alone delayed the time for tumors to regrow by about 30% and the combination at lower doses (one half the dose of either drug alone) delayed the start of regrowth by more than 100%," Dr. Zheng reported.
"The agents appear to work by inhibiting a signal transduction pathway that is important for the growth of these cancer cells," Dr. Zheng added in a conference statement.
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