IADR Abstract Archives
The effects of aromatase inhibitor on gingival cells.
Objectives: Gingival overgrowth is an unwanted side effect caused by various drugs such as antihypertensive drugs, immunosuppressants or anticonvulsants. Recently, we treated a patient aged 70s with chief complaint of rare edematous gingival overgrowth after taking aromatase-inhibitor for treatment of breast cancer in postmenopausal women. Since little has been reported that aromatase-inhibitors induce gingival overgrowth, we investigated the effects of aromatase-inhibitor (anastrozole) on cellular functions of human gingival fibroblasts (HGF) and endothelial cellsin vitro.
Methods: HGF and human umbilical vein endothelial cells (HUVEC) were utilized in this study. Aromatase expression was examined by real-time PCR and western-blotting. The effects of anastrozole on proliferation of HGF were examined by WST-1 assay. Then we evaluated expression of extracellular matrices (ECM), various proteases and cathepsins in HGF by real-time PCR and ELISA. Vascular permeability of HUVEC was examined by FITC-dextran permeability assay, and expression of endothelial barrier proteins was examined by real-time PCR, immunocytochemistry and flow cytometry.
Results: Aromatase expression was detected in both HGF and HUVEC. Anastrozole promoted proliferation of HGF. Stimulation with anastrozole increased the expression of collagen type1α1, collagen type3 α1, fibronectin and decorin, whereas MMP-1, 3 and cathepsin-B mRNA expressions were significantly decreased in anastrozole-treated HGF. Further, stimulation with anastrozole exacerbated vascular permeability of HUVEC. Expressions of VE-cadherin, occludin and ZO-1 in HUVEC were significantly down-regulated in the presence of anastrozole.
Conclusions: Aromatase-inhibitor stimmulated proliferation and ECM expressions in HGF and reduced the expression of MMPs and cathepsin B. These data demonstrate that aromatase-inhibitor may cause impaired metabolism in gingival connective tissues. The increased vascular permeability caused by aromatase-inhibitor possibly reflects edematous gingival overgrowth observed in the patient. Taken together, our study suggested that aromatase-inhibitor may induce “drug-induced gingival overgrowth”.
Methods: HGF and human umbilical vein endothelial cells (HUVEC) were utilized in this study. Aromatase expression was examined by real-time PCR and western-blotting. The effects of anastrozole on proliferation of HGF were examined by WST-1 assay. Then we evaluated expression of extracellular matrices (ECM), various proteases and cathepsins in HGF by real-time PCR and ELISA. Vascular permeability of HUVEC was examined by FITC-dextran permeability assay, and expression of endothelial barrier proteins was examined by real-time PCR, immunocytochemistry and flow cytometry.
Results: Aromatase expression was detected in both HGF and HUVEC. Anastrozole promoted proliferation of HGF. Stimulation with anastrozole increased the expression of collagen type1α1, collagen type3 α1, fibronectin and decorin, whereas MMP-1, 3 and cathepsin-B mRNA expressions were significantly decreased in anastrozole-treated HGF. Further, stimulation with anastrozole exacerbated vascular permeability of HUVEC. Expressions of VE-cadherin, occludin and ZO-1 in HUVEC were significantly down-regulated in the presence of anastrozole.
Conclusions: Aromatase-inhibitor stimmulated proliferation and ECM expressions in HGF and reduced the expression of MMPs and cathepsin B. These data demonstrate that aromatase-inhibitor may cause impaired metabolism in gingival connective tissues. The increased vascular permeability caused by aromatase-inhibitor possibly reflects edematous gingival overgrowth observed in the patient. Taken together, our study suggested that aromatase-inhibitor may induce “drug-induced gingival overgrowth”.