Verapamil이 켈로이드 섬유모세포의 성장과 세포자멸사에 미치는 영향

The Effects of Verapamil on Growth and Apoptosis of Keloid Fibroblast

In this study, the effects of verapamil on growth rate, apoptosis, production of transforming growth factor (TGF-${\beta}$) and fibronectin were evaluated in keloid and normal human dermal fibroblasts. Both fibroblasts were primarily cultured from earlobe keloids of three female patients and treated with various concentrations of verapamil. Cell toxicity was assessed by MTT assay, growth rate and apoptosis by FACS, and the production of TGF-${\beta}$ and fibronectin by ELISA and Western blot, respectively. In the $MTT_{50}$, the cell growth was more suppressed in keloid fibroblasts. In the $MTT_{90}$, cell growth was more stimulated in normal fibroblasts. No significant effect appeared on TGF-${\beta}$ expression but an increase in extracellular fibronectin secretion was found in keloid fibroblasts. Keloid fibroblasts responded to verapamil more sensitively, and the percentage of apoptosis was higher at the $MTT_{50}$l. In brief, verapamil had growth-inhibitory effect with inducing apoptosis at the $MTT_{50}$, but rather growth-stimulatory effect at the $MTT_{90}$. The biphasic effect of verapamil depending on the dose might explain one of the reasons of relapse after keloid treatment with verapamil. Clinical application with high concentration (2.5 mg/ml) is advised unless excessive dosage is used.