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Common anti-inflammatory coaxes liver cancer cells to commit suicide
Date:5/16/2011

s function.

"Normally, STAT3 is persistently activated in cancer cells. If you have a good molecule that sticks to STAT3, it will prevent its activation," Li said. And when STAT3 is inhibited, cellular survival pathways are blocked that cause the cancer cell to chop itself up and die.

The research appears online and is scheduled for later print publication in the journal Cancer Prevention Research.

The biological portion of the study further defined the role of a pro-inflammatory protein in liver cancer's development. The protein, called interleukin-6, or IL-6, is a cytokine, a chemical messenger that causes inflammation, which can have both beneficial and damaging effects in the body. Previous research by other scientists has shown that high levels of IL-6 in the blood are associated with hepatocellular carcinoma, the most common type of liver cancer.

Lin and colleagues determined that IL-6 initiates a chemical reaction called phosphorylation of STAT3. That reaction activates STAT3 inside liver cancer cells, where STAT3 in turn activates at least three other known genes that allow the cells to resist the effects of chemotherapy.

The scientists treated five different types of hepatocellular carcinoma cells with two different doses of celecoxib for two hours, and followed by giving them IL-6 for 30 minutes. The pre-treatment with the lower dose of celecoxib inhibited IL-6's ability to start the reaction that activates STAT3. The higher dose blocked STAT3 altogether.

The researchers then treated a line of liver cancer cells with celecoxib in combination with two chemotherapy drugs: doxorubicin, which is used to treat breast, ovarian, gastric, thyroid and several other cancers, and sorafenib, which is the only chemotherapy medication approved by the Food and Drug Administration for liver cancer treatment. Its brand name is Nexavar.

With both drugs, the addition of celecoxib treatment reduced the numb
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Contact: Jiayuh Lin
lin.674@osu.edu
614-722-5086
Ohio State University
Source:Eurekalert

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