Enhanced expression of membrane transporter and drug resistance in keloid fibroblasts
Enhanced expression of membrane transporter and drug resistance in keloid fibroblasts
复制标题
瘢痕疙瘩成纤维细胞膜转运蛋白表达增强和耐药性
DOI：
10.1016/j.humpath.2011.12.026
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发表时间：
2012-11-01
期刊：
影响因子：
3.3
通讯作者：
Liu, Wei
中科院分区：
文献类型：
--
作者：
Song, Nan;Wu, Xiaoli;Liu, Wei
瘢痕疙瘩的治疗抵抗和高复发率的机制仍不清楚。本研究旨在探讨瘢痕疙瘩与正常成纤维细胞耐药性的差异。将来自9名瘢痕疙瘩患者和9名皮肤供体的成纤维细胞随机组合成3个瘢痕疙瘩细胞池（每个池3例）和3个正常细胞池（每个池3例），并比较它们对长春新碱和米托蒽醌的抗性以及相关分子表达。结果显示，瘢痕疙瘩细胞对长春新碱和米托蒽醌的耐药性较强，存活率高于正常细胞（P <0.05）。维拉帕米可在很大程度上消除瘢痕疙瘩成纤维细胞的耐药性。此外，第1代瘢痕疙瘩成纤维细胞中多药耐药1、ABCB 5（P-糖蛋白家族成员）和细胞色素P450 3A4（但不包括ABCG 2（ATP结合盒转运蛋白））的信使RNA表达水平显著高于第1代正常成纤维细胞;后几代无显著差异。免疫组化染色显示瘢痕疙瘩组织中多药耐药1阳性细胞（圆形）明显多于正常皮肤（多为梭形）（P <0.05），但两组阳性细胞百分比无显著差异。膜转运蛋白的表达增强和对化疗药物的耐药性增加可能是瘢痕疙瘩对治疗的耐药性和治疗后高复发率的原因。(C)2012 Elsevier Inc. All rights reserved.
The mechanisms of keloid resistance to therapy and high recurrence rate remain undefined. This study explored the difference in drug resistance between keloid and normal fibroblasts. Fibroblasts derived from 9 patients with keloid and 9 skin donors were randomly combined into 3 keloid cell pools (3 cases per pool) and 3 normal cell pools (3 cases per pool) and were compared for their resistance to vincristine and mitoxantrone and related molecule expression. The results revealed stronger resistance to both vincristine and mitoxantrone with a higher survival rate in keloid cells than in normal cells (P < .05). The resistance of keloid fibroblasts could be largely abrogated by verapamil treatment. In addition, messenger RNA expression levels of multiple-drug resistance-1, ABCB5 (P-glycoprotein family member), and cytochrome P450 3A4 but not ABCG2 (ATP-binding cassette transporter) were significantly higher in passage 1 keloid fibroblasts than in passage 1 normal fibroblasts; no significant difference was found in latter passages. Immunohistochemistry staining revealed significantly more multiple-drug resistance-1-positive cells (round) in keloid tissue than in normal skin (mostly spindle shaped) (P < .05) but no significant difference in the percentage of positive cells in the 2 groups. Enhanced expression of membrane transporters and increased resistance to chemotherapy agents may contribute to the keloid's resistance to therapy and the high posttherapy recurrence rate. (C) 2012 Elsevier Inc. All rights reserved.