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 : Matsumoto R. et. al., Scientific Reports, Oct. 4, 2016)
Researchers in Japan have discovered that a nonsteroid anti-inflammatory drug (NSAID) used for treating colds suppresses the spread of bladder cancers and reduces their chemoresistance in mice, raising hopes of a future cure for advanced bladder cancers.
This NSAID is called "flufenamic acid" and researchers have discovered it's an inhibitory factor for the metabolic enzyme "aldo-keto reductase 1C1 (AKR1C1)" that's present in high levels in metastatic tumors.
Researchers said inoculating flufenamic acid into cancerous bladder cells suppressed the cells' invasive activities and restored the effectiveness of anticancer drugs.
The discovery of flufenamic acid's usefulness in conjunction with anticancer drugs was made by a team from the Department of Renal and Genitourinary Surgery at Hokkaido University in Japan. It's expected to spur clinical tests aimed at improving prognoses for bladder cancer patients.
Flufenamic acid is used for treating common colds but isn't widely used or available in the United States. It is, however, available in generic form in some Asian and European countries. The drug has been linked to a high rate of gastrointestinal side effects.
Latest cancer treatments use expensive molecular-targeted drugs, a disadvantage for both the patient and his country's health system.
"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 Dr. Shinya Tanaka of the research group.
In the latest research, human bladder cancer cells labeled with luciferase were inoculated into mice, creating a xenograft bladder cancer model. The primary bladder xenograft gradually grew After 45 days, metastatic tumors were detected in the lungs, liver and bone.
By using a microarray analysis (including more than 20,000 genes for the metastatic tumors) the team discovered a three- to 25-fold increase in AKR1C1. They also found high levels of AKR1C1 in metastatic tumors removed from 25 cancer patients, proving the phenomena discovered in the mice also occurs in the human body.
Along with anticancer drugs, an inflammatory substance produced around the tumor, such as interleukin-1β, increased the enzyme levels.
Researchers also identified, for the first time, that AKR1C1 enhances tumor-promoting activities and proved the enzyme blocks the effectiveness of cisplatin and other anticancer drugs.
Bladder cancer is the seventh most common cancer in males worldwide. Every year, about 20,000 people in Japan are diagnosed with bladder cancer, of whom around 8,000 (mostly men) succumb to the disease.
Bladder cancers can be grouped into two types: non-muscle-invasive cancers, which have a five-year survival rate of 90 percent, and muscle-invasive cancers, which have poor prognoses.
The latter are normally treated with such anticancer drugs as cisplatin, but tend to become chemoresistant and, thus, spread to organs such as the lungs and liver, as well as bone.
