Flufenamic Acid Slows Spread of Bladder Cancer in Mouse Model

By LabMedica International staff writers
Posted on 26 Oct 2016

The enzyme aldo-keto reductase 1C1, which could be suppressed by the anti-cold drug flufenamic acid, was found to be highly active in metastatic human bladder cancer and represents a potent molecular target for treating the disease.

In searching for new approaches for treating bladder cancer, investigators at Hokkaido University (Japan) found that the metabolic enzyme aldo-keto reductase 1C1 (AKR1C1) played an essential role in cancer invasion/metastasis and chemoresistance.

Image: Tumor growth in the xenograft bladder cancer model was monitored using a bioluminescence imaging system. Forty-five days after inoculation, metastatic tumors were detected in the lungs, liver and bone (Photo courtesy of Scientific Reports).

This determination was made by using a mouse xenograft model system. In this system human bladder cancer cells were labeled with the gene for the enzyme luciferase and then inoculated into mice. The resulting cancer cells could be traced by following the spread of the luciferase. After 45 days of growth, the primary bladder xenografts generated metastatic tumors that were detected in the lungs, liver, and bone.

The investigators used microarray analysis of more than 20,000 genes to establish that there was a three- to 25-fold increase in the activity of the metabolic enzyme aldo-keto reductase 1C1 (AKR1C1) in the tumor cells. They also found high levels of AKR1C1 in metastatic tumors removed from 25 cancer patients, proving that the phenomena discovered in the mice also occur in the human body.

The investigators also reported in the October 4, 2016, online edition of the journal Scientific Reports that an inflammatory cytokine, interleukin-1beta, increased AKR1C1 in bladder cancer cell lines. On the other hand, the non-steroidal anti-inflammatory drug, flufenamic acid, antagonized AKR1C1 and decreased the cisplatin-resistance and invasion potential of metastatic bladder cancer.

"This latest research could pave the way for medical institutions to use flufenamic acid -a much cheaper cold drug- which has unexpectedly been proven to be effective at fighting cancers," said senior author Dr. Shinya Tanaka, professor of cancer pathology at Hokkaido University.

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Hokkaido University