Cancer Biology

Prevent Diet-induced Pancreatic Cancer by Stalling Digestive Hormone

A recent research led by the team of researchers from Georgetown University found that the diet-induced pancreatic cancer can be prevented by blocking the digestive hormone.

The risk factor for pancreatic cancer includes chronic inflammation and diabetes which indicates the link between high-fat diet and growth of the pancreatic tumor. This growth in pancreatic cancer is due to the interaction between high dietary fat and a digestive hormone called cholecystokinin (CCK).

This same hormone is linked to obesity. People having a diet composed of mainly saturated fat have a high level of CCK. Previous studies indicate that obesity and high-fat diet together or independently promote pancreatic cancer.

During their study,  researchers conducted their study on mice to analyze the interaction between dietary fat, CCK, and pancreatic cancer cell growth. They fed half of the mice with a high-fat diet while the other half with a normal diet.

In the first study, half of the animals were treated with proglumide, a medication that blocks CCK. In the second study, the mice had tumors lacking CCK. In the third study, the mice were deficient in CCK and had pancreatic tumors.

They observed that the mice which were treated with proglumide and found that less tumor growth as compared to untreated mice, in spite of feeding them with a high-fat diet. They also found no response towards high-fat diet in mice lacking digestive hormone CCK. These outcomes suggest that CCK is needed to stimulate the growth of pancreatic cancer. The high-fat diet fed mice lacking CCK receptors did not show any tumor growth, suggesting that without receptors to bind to, increased CCK from dietary fat is unable to promote cancer.

Proglumide treatment also protected the mice from the development of excessive fibrous tissue (fibrosis) that can be associated with cancer metastases and resistance to chemotherapy.

“Most patients with advanced pancreatic cancer succumb to the disease due to metastases; therefore a compound that blocks metastases, even when the primary tumor size is large, may have clinical significance,” the researchers wrote. “CCK [receptor] blockade may play a role in the treatment and prevention of pancreatic cancer.”

Sandeep Nadella, Julian Burks, Abdulhameed Al-Sabban, Gloria Inyang, Juan Wang, Robin D. Tucker, Marie E Zamanis, William Bukowski, Narayan Shivapurkar, Jill P. Smith. Dietary Fat Stimulates Pancreatic Cancer Growth and Promotes Fibrosis of the Tumor Microenvironment through the Cholecystokinin Receptor. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2018

The BioScientist

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