A cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drug (NSAID) usually prescribed to relieve arthritis pain appears to be an effective treatment for liver cancer. Celecoxib (Celebrex) has been found to trigger the death of liver cancer cells (apoptosis) on its own and in combination with each of two chemotherapeutic agents, sorafenib (Nexavar) and doxorubicin (Adriamycin, Doxil, Rubex, generics).
“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,” noted senior study author Jiayuh Lin, PhD, an associate professor of pediatrics at The Ohio State University in Columbus, in a statement describing the findings. “For clinicians, this research suggests the possibility of a new therapeutic strategy.”
Liver cancer remains one of the most difficult cancers to treat successfully. The relative 5-year survival rate for all stages combined is 10%. As Lin and colleagues noted in their report for Cancer Prevention Research, growing evidence demonstrates a link between chronic liver inflammation and the development of hepatocellular carcinoma (HCC), the most common type of liver cancer. Celecoxib helps control inflammation by inhibiting the enzyme COX-2.
Lin’s team used powerful computing techniques to identify optimal drug-fragment combinations that would attach to the protein STAT3, which enables liver cancer cells to resist the effects of chemotherapy drugs. A database search of FDA-approved drugs revealed that celecoxib was structurally similar to the template molecule that would most effectively bind to and inhibit the function of STAT3.
The researchers treated five types of HCC cells with two different doses of celecoxib for 2 hours, and then gave the cells interleukin-6 (IL-6) for 30 minutes. High blood levels of IL-6, a cytokine, have been associated with HCC, and Lin and colleagues learned that IL-6 activates STAT3 within liver cancer cells.
Pretreatment with the lower doses of celecoxib inhibited the ability of IL-6 to initiate the reaction that activates STAT3. The higher dose of celecoxib blocked STAT3 altogether. In addition, when celecoxib was added to sorafenib (the only drug approved by the FDA for liver cancer treatment) or to doxorubicin (used in the treatment of several cancers including breast, ovarian, gastric, and thyroid), the number of viable liver cancer cells were reduced by anywhere from approximately 50% to more than 90%, depending on the doses.