Anti-Diabetes Drugs Has Pancreatic Cancer-Fighting Properties

The oral anti-diabetic thiazolidinediones (TZDs), such as rosiglitazone and pioglitazone could offer a valuable complement to conventional chemotherapy for pancreatic cancer. TZDs appear to have a two-pronged cancer-fighting effect, they note, both blocking cancer growth by acting on peroxisome proliferators activated receptor gamma (PPAR-gamma) and inhibiting the invasiveness of pancreatic cells independently of PPAR-gamma activation.

Dr. A. Galli of the University of Florence and colleagues observe that recent studies have found PPAR-gamma mutations in human cancers, and TZDs — which are known to be PPAR-gamma ligands — have been shown to have anti-cancer effects in certain cell lines. However, "the effect of TZDs on the invasiveness and metastatic potential of pancreatic cancer cells remains unknown."

To investigate, they conducted a series of experiments in pancreatic carcinoma cell lines and pancreatic adenocarcinomas. Seven of the 10 cell lines and 23 of the 42 adenocarcinoma samples showed PPAR-gamma activation. Treating cells in Matrigel-coated invasion chambers inhibited their invasiveness regardless of whether or not the cells expressed PPAR-gamma, and did so in a dose-dependent fashion. However, TZD treatment only inhibited growth of PPAR-gamma-expressing cell lines.

In both PPAR-gamma and non- PPAR-gamma-expressing cell lines, TZD treatment reduced the gelatinolytic activity in metalloproteinase-2 (MMP-2), which plays a major role in pancreatic cancer cell invasion. The fibrinolytic system, another central player in tumor progression, also was inhibited by TZD treatment independent of PPAR-gamma activity. "This effect was correlated with a dramatic upregulation of plasminogen activator inhibitor PAI-1, the major physiological inhibitor of fibrinolysis," the researchers note.

"In conclusion, it is tempting to postulate that TZD have a dual pharmacological effect on pancreatic cells," Dr. Galli and colleagues write. Moreover, they conclude, "these drugs may have application for prevention and treatment of pancreatic cancer in humans." Gut 2004;53:1688-1697

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FACT:

Metoprolol CR / XL Does Not Impair Glucose & Insulin Levels: New data from a clinical trial was presented Monday at a Canadian cardiology meeting. The results show that metoprolol CR/XL, a beta-blocker widely used for the treatment of hypertension and heart failure, does not impair glucose and insulin levels. Lancet 1999;353: 2001-7.