Matrix Metalloproteinase-8 Mediates the Unfavorable Systemic Impact of Local Irradiation on Pharmacokinetics of Anti-Cancer Drug 5-Fluorouracil

• DOI: 10.1371/journal.pone.0021000
• Publication Date: 2011-06-17T21:03:25Z
• Authors: Chen-Hsi Hsieh; Chia-Yuan Liu; Yen-Ju Hsieh; Hung-Chi Tai; Li-Ying Wang; Tung-Hu Tsai; Yu-Jen Chen
• Keywords: Blood plasma

Concurrent chemoradiation with 5-fluorouracil (5-FU) is widely accepted for cancer treatment. However, the interactions between radiation and 5-FU remain unclear. Here, we evaluated influence of local irradiation on pharmacokinetics in rats. The single-fraction was delivered to whole pelvic fields Sprague-Dawley rats after computerized tomography-based planning. at 100 mg/kg prescribed 24 hours radiation. A high-performance liquid chromatography system used measure blood. Matrix metalloproteinase-8 (MMP-8) inhibitor I administered examine whether or not RT modulation pharmacokinetic parameters could be blocked. Compared sham-irradiated controls, reduced area under concentration versus time curve (AUC) plasma and, contrast, increased bile a dose-dependent manner. Based protein array analysis, amount MMP-8 by (2.8-fold 0.5 Gy 5.3-fold 2 Gy) comparison controls. Pretreatment reversed effect AUC plasma. Our findings first indicate that modulate systemic through stimulating release MMP-8. during concurrent chemoradiaiton therapy should rechecked optimal dose reevaluated, adjusted if necessary, CCRT.