title: Enhanced expression of membrane transporter and drug resistance in keloid fibroblasts.
abstract: 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.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Shanghai 9th People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Song
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wu
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gao
authors.forename: Guangdong
authors.initials: G
authors.lastname: Zhou
authors.forename: Wen Jie
authors.initials: WJ
authors.lastname: Zhang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism; D004351:Drug Resistance / Q000187:drug effects / Q000235:genetics*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007627:Keloid / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008942:Mitoxantrone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D012867:Skin / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014750:Vincristine / Q000494:pharmacology; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; C480744:ABCB5 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000972:Antineoplastic Agents, Phytogenic; D012333:RNA, Messenger; D014750:Vincristine; D008942:Mitoxantrone; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human