Researchers used an analytical tool that allows compositional analysis of single lipid droplets in living cells.
Scientists have for the first time shown that controlling cholesterol metabolism could reduce pancreatic cancer spread to other organs, an advance that may lead to a new treatment for the deadly disease using atherosclerosis drugs.
The findings suggest a class of drugs previously developed to treat atherosclerosis could be repurposed for treatment of pancreatic cancer and other forms of cancer, researchers said. "We show for the first time that if you control the cholesterol metabolism you could reduce pancreatic cancer spread to other organs," said Ji-Xin Cheng from Purdue University in the US. Atherosclerosis is the buildup of fats, cholesterol and other substances in arteries, restricting blood flow.
Researchers found accumulations of the compound cholesteryl ester in human pancreatic cancer specimens and cell lines, demonstrating a link between cholesterol esterification and metastasis. Esterification is a biochemical process that allows cholesterol to be stored in cells. Excess quantities of cholesterol result in cholesteryl ester being stored in lipid droplets within cancer cells. "The results of this study demonstrate a new strategy for treating metastatic pancreatic cancer by inhibiting cholesterol esterification," said Jingwu Xie from Indiana University in the US.
"We identified an aberrant accumulation of cholesteryl ester in human pancreatic cancer specimens and cell lines. Depletion of cholesterol esterification significantly reduced pancreatic tumour growth and metastasis in mice," said Junjie Li from Purdue University.
Researchers used an analytical tool called Raman spectromicroscopy that allows compositional analysis of single lipid droplets in living cells. Findings show that drugs like avasimibe, previously developed for treatment of atherosclerosis, reduced the accumulation of cholesteryl ester, researchers said.The disease usually kills within a few months of diagnosis. It is hoped the potential new treatment might extend life of pancreatic cancer patients for a year.
Researchers analysed tissue samples from pancreatic cancer patients and then tested the drug treatment in a type of laboratory mice referred to as an orthotopic mouse model. Specimens of human pancreatic tissues were obtained. Imaging showed a decrease of the number of lipid droplets, and Raman spectral analysis verified a significant reduction of cholesteryl ester in the lipid droplets, suggesting that avasimibe acted by blocking cholesterol esterification, researchers said.
Findings also showed that blocking storage of cholesteryl ester causes cancer cells to die, specifically due to damage to the endoplasmic reticulum, a workhorse of protein and lipid synthesis, they said.
The findings were published in the journal Oncogene.
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