배양된 사람 코점막 섬유아세포에 대한 마이토마이신 C와 5-플루오로우라실의 효과
Effect of Mitomycin C and 5-Fluorouracil on Cultured Human Nasal Mucosa Fibroblasts
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목적: 항대사물질인 mitomycin C (MMC)와 5-fluorouracil (5-FU)이 각각 배양된 사람 코점막 섬유아세포의 증식에 미치는 효과에 대 해 알아보고자 하였다. 대상과 방법: 배양된 사람 코점막 섬유아세포를 여러 농도의 MMC와 5-FU에 각각 5분간 노출시키고, 대조군은 약물 처치 없이 DMEM 배지에만 노출시켰다. 위상차 현미경으로 섬유아세포의 형태학적 관찰 후 세포의 생존율은 MTT assay로, 세포 자가사멸은 Acridine orange/Hoechst (AO/HO) 염색법으로 평가하였다. 결과: MMC와 5-FU에 노출된 두 실험군 모두에서 섬유아세포는 정상적인 방추형 모양을 잘 유지하였고, MTT assay 결과상 약물 농도 의존적으로 섬유아세포의 증식을 억제시켰다. 또한, AO/HO 염색 시 두 실험군 모두에서 자가소멸 세포가 관찰되었다. 결론: MMC와 5-FU는 모두 생체 외 환경에서 섬유아세포에 대해 항증식 효과를 나타내었고, 세포 자가소멸이 그 기전에 연관성이 있는 것으로 보인다. 따라서 코경유 눈물주머니코안연결술 시 두 약물의 보조적 사용은 코점막 증식을 억제함으로써 수술 결과를 향상 시킬 수 있을 것이다.
Abstract
Purpose: To investigate the effects of two antimetabolites, mitomycin C (MMC) and 5-fluorouracil (5-FU), on proliferation of cultured human nasal mucosa fibroblasts. Methods: Human nasal mucosa fibroblasts were primarily cultured, and exposed to various concentrations of MMC and 5-FU for 5 minutes. Control fibroblasts were exposed to only DMEM media without the drugs. Effect of drugs on cell morphology was observed by phase-contrast microscopy. Cell viability and apoptosis were measured using MTT [3-(4,5-dimethylthiazol- 2-yl)-2,5-diphenyl-tetrazolium bromide] assay and Acridine orange/Hoechst (AO/HO) staining, respectively. Results: In both experimental groups exposed to MMC and 5-FU, fibroblasts maintained standard spindle shape. The MTT assay showed that both MMC and 5-FU inhibited fibroblast proliferation in a dose dependent manner. AO/HO staining showed apoptotic cells in both experimental groups. Conclusions: Both MMC and 5-FU have an antiproliferative effect on fibroblasts in vitro at least through induction of apoptosis. Therefore, adjuvant use of either MMC or 5-FU during endonasal dacryocystorhinostomy may improve the clinical outcome by inhibiting proliferation of the nasal mucosa.
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