Drug Combo Slows Prostate Cancer Growth

Researchers seeking drugs to slow or prevent the growth of prostate tumors have found that a cocktail comprising the active form of vitamin D, calcitriol, along with a nonspecific NSAID (nonsteroidal anti-inflammatory drug) such as ibuprofen or naproxen effectively inhibited growth of prostate cancer cells in culture. The combination of calcitriol and a NSAID synergistically acted to achieve significant prostate cancer cell growth inhibition at drug concentrations two to ten times lower than was found when each drug was used separately.

After determining that the mixture of calcitriol and NSAID reduced prostate cancer cell growth in culture by up to 70%, investigators at Stanford University (Palo Alto, CA, USA) used cDNA microarray technology to determine what the drug combination was doing to the cells at the genetic level. They reported in the September 1, 2005, issue of Cancer Research that the drugs lowered prostaglandin production in two ways. They significantly repressed the mRNA and protein expression of prostaglandin endoperoxide synthase/cyclooxygenase-2 (COX-2), the key prostaglandin synthesis enzyme, and they also up-regulated the expression of 15-hydroxyprostaglandin dehydrogenase, the enzyme initiating prostaglandin catabolism.

"There is great enhancement when the drugs are given together, using what we think is a safe dose in humans,” said senior author Dr. David Feldman, professor of medicine at Stanford University. "It is hard to make an exact comparison, as we are talking about cells in a dish and not a person.” Dr. Feldman emphasized that calcitriol is a prescription-only drug. "We do not want patients to think that if they take over-the-counter vitamin D, it will work in the same way.”