MONDAY, June 15, 2009 (HealthDay News) -- In a study of mice with lung cancer, a treatment that targeted nicotine receptors more than doubled the animals' survival time, Italian researchers say.
Nicotine plays a dual role in lung cancer. Changes in genes encoding nicotine receptors not only drive the urge the smoke, but also increase susceptibility to lung cancer. Exposure to nicotine boosts the expression of nicotine receptors, which leads to increased cell proliferation and inhibits the programmed cell death known as apoptosis.
In the new study, published in the June 15 issue of the American Journal of Respiratory and Critical Care Medicine, the compound α-CbT dampened the expression of nicotine receptors and increased apoptosis, prolonging the lives of the mice.
"This research clearly has profound clinical implications regarding the role of nicotine in stimulating lung cancer and nicotine receptor antagonists in treating the disease," said Dr. John Heffner, past president of the American Thoracic Society, in a news release from the society. Heffner, who was not involved in the research, added, "The highly addictive nature of nicotine, however, complicates patients' ability to quit smoking and avoid ongoing nicotine exposure."
Previous research has shown that it's possible to dampen the response of nicotine acetylcholine receptors (nAChRs) using an antagonist called d-tubocurarine/α-Cobratoxin (α-CbT), which specifically targeted the area most linked to increased cell growth.
In the study, researchers grafted human non-small-cell lung carcinoma (NSCLC) onto the lungs of mice and then delayed treatment, allowing the tumors to become well-established.
The mice were then divided into three groups: the untreated group; the standard chemotherapy drug group; and the α-CbT group.
Mice that were categorized as non-obese/severe combined immunodeficient (NOD/SCID) and treated with cisplatin (the standard chemotherapy agent) were found to have a 16 percent longer median survival time than untreated mice. NOD/SCID mice treated with α-CbT had an increased median survival time of 1.7-fold over the cisplatin-treated mice and 2.1-fold over untreated mice.
"The results of this study show that α-CbT, a powerful, high-affinity α-7-nAChR inhibitor, induces antitumor activity against NSCLC by triggering apoptosis," wrote Patrizia Russo of the Lung Cancer Unit of the National Cancer Research Institute in Genoa, Italy, in the news release.
Noncancerous cells did not appear to be affected by α-CbT, suggesting limited toxicity, the researchers found, but they noted that cancer cells with the most receptor binding sites seemed have the greatest treatment sensitivity.
"The goal of this research line is to explore the widest range of possibilities of intervention on the α7-nAChRs," Russo said. "We hope to move further on towards the clinical setting experimentation phase for the assessment of potentially new treatment strategies for NSCLC."
The U.S. National Cancer Institute has more on non-small-cell lung cancer.