Blood Pressure Drugs Halt Pancreatic Cancer Cell Growth, Jefferson Researchers Find
Researchers
at the Kimmel Cancer Center at Thomas Jefferson University in
Philadelphia are inching closer to understanding how common blood
pressure medications might help prevent the spread of pancreatic
cancer. They have found in the laboratory that one type of
pressure-lowering drug called an angiotensin receptor blocker inhibits
pancreatic cancer cell growth and causes cell death.
In
earlier work in the laboratory, Hwyda Arafat, M.D., Ph.D., associate
professor of Surgery at Jefferson Medical College, and her team showed
that angiotensin receptor blockers may help reduce the development of
tumor-feeding blood vessels, a process called angiogenesis. Other
studies have linked a lower incidence of cancer with the use of
angiotensin blocking therapies. Such drugs, she says, may become part
of a novel strategy to control the growth and spread of cancer.
One
of these drugs – AT1R (Ang II type 1 receptor) blockers – inhibit the
function of the hormone angiotensin II (Ang II) in the pancreas. The
receptor is expressed in pancreatic cancer cells. Ang II increases the
production of VEGF, a vascular factor that promotes blood vessel growth
in a number of cancers. High VEGF levels have been correlated with poor
cancer prognosis and early recurrence after surgery. Dr. Arafat’s
research team has shown that AngII indirectly causes VEGF expression by
increasing AT1R expression.
Dr.
Arafat’s group explored the effects of blocking AT1R on the pancreatic
cancer cell reproductive cycle and programmed cell death, or apoptosis,
and the mechanisms involved. It 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.” The team reports its findings
April 14, 2008 at the annual meeting of the American Association for
Cancer Research in San Diego.
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,” she notes.
“This
is really exciting because the role of this receptor has never been
known,” Dr. Arafat says. “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.” Ultimately, the group hopes to
be able to test these agents in human trials, she says.
Pancreatic
cancer, the fourth-leading cause of cancer death in this country, takes
some 34,000 lives a year. The disease is difficult to treat,
particularly because it is frequently detected after it has spread to
other areas on the body. Only 4 percent of all individuals with
pancreatic cancer live for five years after diagnosis, and
approximately 25 percent of those diagnosed with pancreatic cancer who
undergo successful surgical removal of their disease live at least that
long.
Media Only Contact:
Steve Benowitz
Thomas Jefferson University Hospital
Phone: (215) 955-6300
Published: 4/14/2008