title: ABCB1 Is Upregulated in Acquisition of Taxane Resistance: Lessons from Esophageal Squamous Cell Carcinoma Cell Lines.
abstract: Esophageal cancer is one of the common malignancies worldwide, particularly in eastern African and Asian countries including Japan. Taxane (paclitaxel or docetaxel) is one of the effective chemotherapeutic reagents for patients with esophageal cancer, but acquisition of chemoresistance frequently occurs; this is one of the most frequent causes for therapeutic failure. In this study, we established three taxane resistant esophageal squamous cell carcinoma cell lines and explored possible mechanisms for the acquisition of chemoresistance. Microarray analyses indicated that the ABCB1 (ATP binding cassette subfamily B member 1) gene was significantly upregulated in taxane resistant esophageal cancer cell lines. Moreover, we found that siRNA mediated ABCB1 knockdown successfully restored drug sensitivity in both paclitaxel and docetaxel resistant esophageal cancer cell lines. In conclusion, we propose that ABCB1 might play a pivotal role in acquisition of taxane resistance and could be a promising target for treatment of patients with esophageal cancer after acquisition of taxane resistance.
authors.affiliation: Department of Molecular Pathology, Tohoku University School of Medicine.
authors.forename: Ruobing
authors.initials: R
authors.lastname: Wang
authors.forename: Anton
authors.initials: A
authors.lastname: Sumarpo
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Saiki
authors.forename: Na
authors.initials: N
authors.lastname: Chen
authors.forename: Makoto
authors.initials: M
authors.lastname: Sunamura
authors.forename: Akira
authors.initials: A
authors.lastname: Horii
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D001952:Bridged-Ring Compounds / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004938:Esophageal Neoplasms / Q000235:genetics* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D009154:Mutation / Q000235:genetics; D034741:RNA, Small Interfering / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D001952:Bridged-Ring Compounds; D034741:RNA, Small Interfering; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; C080625:taxane