AACR: Statin-COX2 Inhibitor Combo Slows Prostate Cancer Growth

By Charles Bankhead
SAN DIEGO, 18 April 2008 -- Progression of androgen-independent prostate cancer was significantly inhibited in mice by a combination of atorvastatin (Lipitor) and celecoxib (Celebrex), according to a study reported here. Each drug individually slowed tumor progression from androgen-dependent to androgen-independent status, Xi Zheng, Ph.D., of Rutgers University in New Brunswick, N.J., told attendees at the American Association for Cancer Research meeting. However, he said, the two drugs combined had additive growth-inhibiting activity compared with either drug alone.
"This represents a viable prevention strategy to stop the progression of prostate cancer to androgen-independent status, which is much more aggressive and currently has limited therapeutic options," said Dr. Zheng.
Several clinical studies have shown that chronic treatment with selective cyclooxygenase-2 inhibitors block the formation of precancerous and cancerous lesions. Laboratory and epidemiologic evidence suggest that HMG-CoA reductase inhibitors (statins) prevent carcinogenesis. Additionally, HMG-CoA reductase is upregulated in some types of cancer.
Last year, Dr. Zheng and colleagues reported that the combination of atorvastatin and celecoxib inhibited growth of advanced androgen-independent prostate cancer. The current study carried the investigation to androgen-dependent tumors.
The researchers injected prostate cancer cells into severe combined immunodeficient mice. After four to six weeks, animals that had prostate tumors were surgically castrated and treated for six weeks with intraperitoneal injections of vehicle, celecoxib (10 µg/g/day), atorvastatin (10 µg/g/day), or low doses (5 µg/g/day) of the two drugs.
Animals that received vehicle initially had tumor regression in response to castration, but within two weeks, the tumors had progressed into androgen-independent prostate cancer.
Celecoxib or atorvastatin alone inhibited tumor regrowth and delayed progression to androgen-independent status by about 30% compared with vehicle.
The low-dose combination of atorvastatin and celecoxib demonstrated more potent inhibitory action, delaying the time to tumor progression to androgen-independent status by more than 100% compared with vehicle.
The findings confirmed prior evidence of additive or synergistic anticancer activity of celecoxib and atorvastatin in combination.
Dr. Zheng called for further confirmation through a clinical trial.
Dr. Zheng reported no disclosures.
Primary source: American Association for Cancer ResearchSource reference:Zheng X et al. "Inhibition of androgen-independent growth of LNCaP xenograft tumors in immunodeficient mice by a combination of atorvastatin (Lipitor) and celecoxib (Celebrex)." AACR Meeting 2008. San Diego. Abstract 2100.