Researchers at the Kimmel Cancer Center at Thomas Jefferson University in Philadelphia have found that a blood pressure-lowering drug called an angiotensin receptor blocker inhibits pancreatic cancer cell growth and causes cell death.
In previous studies, Hwyda Arafat, M.D., Ph.D., associate professor of Surgery at Jefferson Medical College, and her colleagues showed that angiotensin receptor blockers might help reduce the development of tumour-feeding blood vessels, a process called angiogenesis.
Other studies have associated a lower incidence of cancer with the use of angiotensin blocking therapies. Arafat said that theses drugs might become part of a novel strategy to control the growth and spread of cancer.
One such drug, AT1R (Ang II type 1 receptor) blockers, inhibits the function of the hormone angiotensin II (Ang II) in the pancreas.
The receptor is expressed in pancreatic cancer cells. Ang II boosts the production of VEGF, a vascular factor that promotes blood vessel growth in a number of cancers.
High levels of VEGF have been linked to poor cancer prognosis and early recurrence after surgery. Dr. Arafat and her team have shown that AngII indirectly causes VEGF expression by boosting AT1R expression.
Researchers investigated the effects of blocking AT1R on the pancreatic cancer cell reproductive cycle and programmed cell death, or apoptosis, and the mechanisms involved.
They found that blocking AT1R inhibited pancreatic cancer cell growth and promoted cell death.
"This happens through inducing the activity of the gene p53, which controls programmed cell death, and also by inhibiting anti-cell death pathways such as those involving the gene bcl-2," Dr. Arafat said.
The researchers also found that blocking AT1R affects p21, a gene that regulates the cell cycle.
"We found that blocking this receptor can cause cell cycle arrest. This is really exciting because the role of this receptor has never been known," Dr. Arafat said.
"It's never been connected to cell division or apoptosis. We're also now further exploring the mechanisms involved. The exciting thing is that this receptor already has so many available pharmaceutical blockers on the market," she added.
She further said that the group hopes to be able to test these agents in human trials.
The findings have been reported on April 14, 2008 at the annual meeting of the American Association for Cancer Research in San Diego.