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06.10.2017


Physical exercise may improve lung cancer survival chances

Physical exercise may improve lung cancer survival chances
Lung cancer is one of the most fatal forms of cancer. Five years after being diagnosed only 15 percent of patients are still alive. That percentage may increase if lung cancer patients get more exercise, suggests an animal study that American oncologists at Emory University published in 2014 in Cancer. According to the study, physical exercise activates the anti-cancer p53 gene, which has become deactivated in many forms of cancer that are difficult to treat.

Study
The researchers injected 20 mice with A549 lung cancer cells [one is shown in the photo] and monitored the growth of the lung cancer tumours by doing scans. The moment the tumours became visible, 10 mice were given a treadmill in their cage [Exercising] and the other 10 were not [Sedentary].

Results
The mice with a treadmill in their cage ran for about an hour a day, we estimate. Running kept the dimensions of the lung cancer tumours stable in these animals, while the tumours in the sedentary mice increased.


Physical exercise may improve lung cancer survival chances

Physical exercise may improve lung cancer survival chances


The researchers found more of the suicide enzyme caspase-3 in the mice that exercised. This enzyme is normally activated by the p53 anti-cancer gene. This gene is damaged in about half of the tumours of people with lung cancer, and in many other tumours the gene no longer functions well because of other damage.

The researchers observed a considerably raised level of activity of the p53 gene in all 10 physically active mice.


Physical exercise may improve lung cancer survival chances


Mechanism
"Mechanistically, tumors from exercising mice exhibit higher levels of p53 and Bax, suggesting that exercise may be increasing p53-driven apoptosis," the researchers wrote. "Apoptosis is the hallmark of p53 tumor suppression; and, in our study, tumors from exercising mice had increased apoptosis with higher levels of active caspase 3."

"In healthy patients, exercise is a known promoter of p53 translocation into the mitochondria in skeletal muscle as well as increased p53 phosphorylation, which is associated with increased protein stability and activity. It is well known that p53 acts as a quintessential tumor suppressor gene by inducing cell-cycle arrest, apoptosis and senescence."

"These results represent novel findings, because increased levels of functional p53 protein were observed in lung tumors from exercising mice. Although A549 lung adenocarcinoma cells do not contain a recognized p53 mutation, our sedentary mouse lung tumors did demonstrate impaired p53 levels, with no measurable p53 protein and a phenotype consistent with a rapidly growing lung tumor. Many p53 wild-type tumors exhibit similar behavior because of increases in negative regulators of p53, such as MDM2."

"Thus, exercise is likely stabilizing wild-type p53 proteins and rendering them more effective at tumor suppression."

Conclusion
"Targeting tumor suppressors by pharmacologic means has proven to be difficult, but exercise appears to be a promising anticancer therapy that improves p53 tumor suppressor function," the researchers continued. "However, further studies are needed to determine whether the mechanism behind exercise-induced tumor reduction is reliant on p53 alone."

"Future research directions include exploratory studies in humans examining the effects of cardiovascular exercise on lung cancer progression."

Source:
Cancer. 2014 Nov 1;120(21):3302-10.

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