title: Monoclonal antibody targeting MUC1 and increasing sensitivity to docetaxel as a novel strategy in treating human epithelial ovarian cancer.
abstract: The purpose of this study was to investigate the in vitro effect of anti-MUC1 monoclonal antibody (MAb) C595 alone and in combination with docetaxel, on the growth and survival of different epithelial ovarian cancer (EOC) cell lines. MUC1 expression was assessed on EOC cell lines (OVCAR-3, IGROV-1, A2780, CAOV-3, TOV-21G, TOV-112D, SKOV-3 and OV-90) using immunofluorescence labeling and flow cytometry. The effect of MAb C595 alone or in combination with docetaxel on the cell lines was studied by proliferation, colony and TUNEL assays. Our results indicate that all primary and metastatic EOC cell lines tested were positive to MAb C595 (MUC1); MAb C595 inhibited EOC cell proliferation in a MUC1- and dose-dependent manner; low-dose MAb C595 (1/2 of IC₅₀) combined with docetaxel greatly improved efficiency of cell killing in EOC cells and induced apoptosis; the additive effect of MAb C595 was further confirmed in colony forming assays; and cell death following single or combined treatments was associated with the release of cytochrome c and increased caspase-3 activity. These results suggest that MAb C595 used either alone, or combined with docetaxel, is an attractive strategy for targeting human EOC.
authors.affiliation: Department of Gynecologic Oncology, Henan Cancer Hospital, Zhengzhou, China. wangli1672003@yahoo.com.cn
authors.forename: Li
authors.initials: L
authors.lastname: Wang
authors.forename: Hongmin
authors.initials: H
authors.lastname: Chen
authors.forename: FengHua
authors.initials: F
authors.lastname: Liu
authors.forename: Michele C
authors.initials: MC
authors.lastname: Madigan
authors.forename: Carl A
authors.initials: CA
authors.lastname: Power
authors.forename: Jingli
authors.initials: J
authors.lastname: Hao
authors.forename: Kate I
authors.initials: KI
authors.lastname: Patterson
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Pourgholami
authors.forename: Philippa M
authors.initials: PM
authors.lastname: O'Brien
authors.forename: Alan C
authors.initials: AC
authors.lastname: Perkins
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002469:Cell Separation; D000077143:Docetaxel; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D020287:In Situ Nick-End Labeling; D018613:Microscopy, Confocal; D018396:Mucin-1 / Q000187:drug effects / Q000378:metabolism*; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000378:metabolism; D043823:Taxoids / Q000627:therapeutic use*
chemical_list: D000911:Antibodies, Monoclonal; D018396:Mucin-1; D043823:Taxoids; D000077143:Docetaxel