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Science Forum Index » Medicine - Cancer Forum » cox-2 inhibitors + statins have potent anti-cancer effect
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 Posted: Mon Apr 14, 2008 1:29 pm |
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http://www.eurekalert.org/bysubject/medicine.php
Public release date: 14-Apr-2008
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Contact: Joseph Blumberg
blumberg@ur.rutgers.edu
732-932-7084 x652
Rutgers University
Celebrex-Lipitor combo may halt prostate cancer
Anti-inflammatory and statin used in tandem can stop progression of disease
NEW BRUNSWICK, N.J. - Researchers at Rutgers' Ernest Mario School of
Pharmacy have shown that administering a combination of the widely used
drugs Celebrex (celecoxib, a nonsteroidal anti-inflammatory drug) and
Lipitor (atorvastatin, a cholesterol lowering drug) stops the transition of
early prostate cancer to its more aggressive and potentially fatal stage.
Prostate cancer is the second leading cause of cancer death in men in the
United States, with more than a quarter-million new cases appearing each
year, according to the American Cancer Society. The findings are being
presented by Rutgers Professor Xi Zheng at the annual meeting of the
American Association for Cancer Research in San Diego, April 14th.
In the early stage of the disease, when it is typically diagnosed, prostate
cancer cells depend on androgen hormones, such as testosterone, to grow.
Treatment at this stage involves either decreasing the production of the
hormone or blocking its actions on the cancer cells.
"Anti-androgen therapy slows the prostate cancer but eventually the cancer
becomes androgen-independent, the therapy becomes ineffective and the cancer
cells become more aggressive," said Xi Zheng, assistant research professor
at Rutgers, The State University of New Jersey, who conducted the study.
"Treatments available for the later stage cancers are not very good," said
Allan Conney, director of Rutgers' Susan Lehman Cullman Laboratory for
Cancer Research, another researcher on the project. "Oncologists employ
classical chemotherapy drugs which are very toxic and don't work all that
well."
Zheng and Conney's research objective was to find a way to indefinitely
delay the transition to androgen-independence, prolonging the time during
which the cancer would be responsive to effective, low-toxicity,
anti-hormone therapy.
Zheng explained that their experiments were first conducted on cell cultures
in the laboratory, where the researchers tested the effects of the drugs on
the growth of prostate cancer cells from four different cell lines. They
then moved on to test the drugs on specially bred mice in which prostate
cancer tumors were introduced under the skin. Celebrex alone, Lipitor alone,
and the two in combination were tested at the lab bench and on the mice.
"A combination of low doses of Lipitor and Celebrex had a more potent
inhibiting effect on the formation of later stage tumors than a higher dose
of either agent alone," Zheng reported. "The results from our study indicate
that a combination of Lipitor and Celebrex may be an effective strategy for
the prevention of prostate cancer progression from the first to the second
stage."
Zheng also noted that the team is exploring the underlying molecular
mechanisms to understand how Lipitor and Celebrex work on prostate cancer,
perhaps identifying an important signaling pathway for tumor cell growth
that the drugs inhibit.
Conney pointed out that previous experiments reported in the Sept. 15, 2007,
issue of Clinical Cancer Research had demonstrated that the Lipitor-Celebrex
combination also inhibited the growth of prostate cancer cells in the later
androgen-independent stage.
"So if you can affect the early stage and prevent it from becoming the more
severe form, that's a good thing. If you can also inhibit the growth of the
more severe form, that's also a good thing," Conney said.
Human clinical trials are being planned at the Robert Wood Johnson Medical
School of the University of Medicine and Dentistry of New Jersey in New
Brunswick.
"If the clinical trials go well, we could have something available in five
years, but it would be nice to speed that up," Conney said. "If the trials
show that the drug therapy does a good job of preventing the cancer from
advancing, we won't need to worry about how to handle the more aggressive
later stage cancer.
"This is something we hope is going to save lives," he added.
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