title: Overexpression of Lewis(y) antigen protects ovarian cancer RMG-1 cells from carboplatin-induced apoptosis by the upregulation of Topo-I and Topo-II β.
abstract: Lewis (y) antigen, a difucosylated oligosaccharide, has been shown to be associated with malignant properties of ovarian carcinomas. In this study, we have investigated the potential role of Lewis (y) antigen, which was stably transfected into ovarian cancer RMG-1 cells, on carboplatin-induced apoptosis. Overexpression of Lewis (y) antigen effectively protected vitronectin-adherent RMG-1 cells from carboplatin-induced apoptosis as assessed by Hoechst 33258 staining and flow cytometry. Treatment with anti-Lewis (y) antigen, anti-integrin αv, or anti-integrin β3 antibody partially abolished the protective effect on apoptosis and markedly inhibited the expression of Topo-II β in cells overexpressing Lewis (y) antigen (all P < 0.01). Moreover, elevated expression of Topo-I and Topo-II β was found in Lewis (y) antigen-overexpressing cells (P < 0.01). However, no obvious changes in Topo-II α were observed throughout the study (P > 0.05). Taken together, these data suggest that the overexpression of Lewis (y) antigen confers cell adhesion-mediated drug resistance to apoptosis in ovarian cancer cells by the upregulation of Topo-I and Topo-II β. Therefore, the inhibition of Lewis (y) antigen may be a novel strategy of cancer chemotherapy.
authors.affiliation: Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang 110004, People's Republic of China.
authors.forename: Changzhi
authors.initials: C
authors.lastname: Wang
authors.forename: Limei
authors.initials: L
authors.lastname: Yan
authors.forename: Yifei
authors.initials: Y
authors.lastname: Wang
authors.forename: Bei
authors.initials: B
authors.lastname: Lin
authors.forename: Shuice
authors.initials: S
authors.lastname: Liu
authors.forename: Quanrong
authors.initials: Q
authors.lastname: Li
authors.forename: Lili
authors.initials: L
authors.lastname: Gao
authors.forename: Shulan
authors.initials: S
authors.lastname: Zhang
authors.forename: Masao
authors.initials: M
authors.lastname: Iwamori
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D016190:Carboplatin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000096:biosynthesis* / Q000235:genetics; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000096:biosynthesis*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000517:prevention & control; D000075223:Poly-ADP-Ribose Binding Proteins; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology*
chemical_list: D004268:DNA-Binding Proteins; D007983:Lewis Blood Group Antigens; C094162:Lewis Y antigen; D000075223:Poly-ADP-Ribose Binding Proteins; D016190:Carboplatin; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II; C000618814:TOP2B protein, human