Celecoxib aids self-destruction of liver cancer cells
Celecoxib, sold under the brand name Celebrex, promotes suicide of liver cancer cells.
The drug is a nonsteroidal anti-inflammatory drug, commonly known as NSAID. Celecoxib inhibits an enzyme known as cyclooxygenase-2 that promotes inflammation.
Research led by Jiayuh Lin, an associate professor of pediatrics at Ohio State University, at Ohio State University found the drug interacts with a protein, causing liver cancer cells to self-destruct.
Celecoxib binds to the STAT3 gene inside the cancer cells, rendering the gene inactive. The gene helps cancer cells resist chemotherapy.
Lin found the anti-cancer property of Celebrex by using computational models to find structures that would bind to proteins and block their activity in cancer cells.
The anti-inflammatory drug was chosen from a database of federally approved drugs because it fit the structural profile of template molecule that would bind to STAT3.
Lin explained STAT3 is always active in cancer cells. Molecules that stick to the gene prevent it from activating.
“And when STAT3 is inhibited, cellular survival pathways are blocked that cause the cancer cell to chop itself up and die”, Lin said.
Celebrex added to chemotherapy drugs reduces number of cancer cells
The researchers looked at how celexicob affects interleukin-6 (IL-6)that can be pro-inflammatory and found in high levels with liver cancer.
IL-6 starts a chemical reaction that activates STAT3 and 3 other genes that make liver cancer resist treatment with chemotherapy drugs.
In the lab, liver cancer cells were pre-treated with celecoxib and then the researchers added IL-6.
Two different doses of Celebrex were used. The higher dose blocked the activity of STAT3 completely.
Next, they added celecoxib to two FDA approved chemotherapy drugs. One drug, doxorubicin, treats breast, ovarian, stomach and thyroid cancer. The other drug, sorafenib, or Nexavar, is the only approved chemotherapy agent for liver cancer.
The combination of the two drugs, combined with celexicob reduced the number of liver cancer cells from 50 to 90 percent.
“Each chemotherapy drug alone will reduce the growth of cancer cells, but when each single drug is combined with Celebrex, a greater growth suppression effect was observed”, explains Lin.
Lin says the combination should kill liver cancer cells more quickly than either alone. The drug is recently studied as a breast cancer treatment that shows promise.
Identifying the anti-inflammatory’s drug molecular structure and its ability to bind with STAT3 is the first step.
Lin says because the experiment was done in the lab, the next step is to ensure it will work in humans. Celecoxib is also being explored for other types of cancer treatment because if its ability to bind to STAT3 and cause cancer cell death.
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