Blood Pressure Drug Shrinks Lung Cancer Tumors In Mice

Reporting in the journal Cancer Research, the scientists said that in mice treated with the hormone, angiotensin-(1-7), tumor volume decreased by 30 percent. In mice that did not receive the treatment, the tumor size more than doubled.

Patricia E. Gallagher, Ph.D., and E. Ann Tallant, Ph.D., senior researchers on the project, had previously reported a similar effect in lung cancer cells studied in the laboratory.

"The current study is the first demonstration of the effect in animals," said Tallant. "Taken together, the two studies suggest a novel treatment for lung cancer, a disease that kills an estimated 170,000 Americans each year."

Wake Forest's Comprehensive Cancer Center will begin studies of the hormone in cancer patients.

"We hope that our clinical trials of angiotensin-(1-7) will lead to the identification of an effective new cancer treatment for our patients," said Frank M. Torti, M.D., M.P.H., director of the Cancer Center, which helped fund the early development of angiotensin (1-7) as an anticancer treatment.

Lung cancer is the leading cause of death in developed countries, accounting for about 170,000 new cases each year in the U.S. In almost two-thirds of cases, the cancer has spread to the lymph nodes by the time of diagnosis, reducing the chances of successful treatment. The five-year survival rate for lung cancer is about 14 percent, the researchers said.

"This grim prognosis indicates a continued need for novel treatment approaches to reduce lung cancer deaths," said Gallagher.

The idea to evaluate the effects of angiotensin-(1-7) on lung cancer came from studies observing that rates of lung cancer were lower in people whose high blood pressure was treated with angiotensin-converting enzyme (ACE) inhibitors. These drugs, which include Capoten® and Lotensin®, increase levels of angiotensin-(1-7) in the bloodstream.

Gallagher and Tallant have been working with angiotensin -(1-7) for years as members of the Hypertension and Vascular Research Center faculty. Carlos M. Ferrario, M.D., center director, discovered angiotensin-(1-7) in 1988, and found it to be a critical element of the blood pressure control system. The hormone relaxes (dilates) the walls of the blood vessels, causing blood pressure to be lowered. ACE inhibitors may work by increasing angiotensin-(1-7).

For the current study, human cancer cells were obtained from the American Tissue Culture Collection. Mice were inoculated with the cells and 32 days later were randomly selected to receive either an intravenous treatment of angiotensin-(1-7) or saline for 28 days. The blood levels of angiotensin-(1-7) achieved through treatment were similar to levels in humans being treated with an ACE inhibitor.

"The study may explain the molecular mechanism for a decreased risk of lung cancers in patients with high blood pressure taking ACE inhibitors," said Tallant.

The researchers believe that angiotensin-(1-7) reduces cyclooxygenase-2 (COX-2), an enzyme that regulates cell growth. COX-2 is found at higher levels in 70 to 90 percent of malignant lung tumors.

Theoretically, drugs to reduce COX-2 would also be effective at shrinking tumors. But the drugs, such as Vioxx®, have been shown to increase the risk of heart attack, stroke and angina.

The researchers said that additional studies of angiotensin-(1-7) are needed, but that the hormone shows promise as a lung cancer treatment -- either alone or in combination with other drugs.

The research was funded by the National Institutes of Health and the Wake Forest University Comprehensive Cancer Center.

Co-researchers were graduate student Jyotsana Menon, lead author, graduate student David R. Soto-Pantoja, Michael Callahan, Ph.D., J. Mark Cline, D.V.M., and Carlos M. Ferrario, M.D., all from Wake Forest.