title: Role of delta-like ligand-4 in chemoresistance against docetaxel in MCF-7 cells.
abstract: As Notch receptors have been shown to induce chemoresistance, we hypothesized that delta-like ligand-4 (DLL4), a central Notch signalling ligand, might also participate in chemoresistance in breast cancer. To investigate this issue, overexpression of DLL4 was induced by transfection with expression vectors for DLL4 in the human breast cancer cell line Michigan cancer foundation-7 (MCF-7). It was found that DLL4 could be adaptively upregulated by docetaxel (DOC) treatment in a dose-dependent manner, but Notch1 was unaffected. Overexpression of DLL4 could significantly attenuate the cytotoxic effects of DOC by increasing Bcl-2 expression, while decreasing Bax expression, apoptosis rate and DNA damage. The protective effects of DLL4 made cells acquire chemoresistance against DOC and resulted in cancer cell survival. DLL4 is normally regarded as a regulator of vascular development. Our results expanded the understanding of DLL4. Since DLL4 may play an important role in the process of acquiring chemoresistance, it may be a promising target in overcoming chemoresistance in breast cancer.
authors.affiliation: 1 Shiyan Taihe Hospital (affiliated Hospital of Hubei University of Medicine), Hubei, Shiyan, China.|2 HuBei University of Medicine, Hubei Shiyan, China.
authors.forename: Q
authors.initials: Q
authors.lastname: Wang
authors.affiliation: 1 Shiyan Taihe Hospital (affiliated Hospital of Hubei University of Medicine), Hubei, Shiyan, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Shi
authors.affiliation: 3 Centre for Biophotonics, Lancaster Environment Centre, Lancaster University, Bailrigg, Lancaster, UK.
authors.forename: H J
authors.initials: HJ
authors.lastname: Butler
authors.affiliation: 1 Shiyan Taihe Hospital (affiliated Hospital of Hubei University of Medicine), Hubei, Shiyan, China.
authors.forename: J
authors.initials: J
authors.lastname: Xue
authors.affiliation: 1 Shiyan Taihe Hospital (affiliated Hospital of Hubei University of Medicine), Hubei, Shiyan, China.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.affiliation: 4 Ministry of Education, Key Lab of Environment and Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: P
authors.initials: P
authors.lastname: Duan
authors.affiliation: 2 HuBei University of Medicine, Hubei Shiyan, China.
authors.forename: H
authors.initials: H
authors.lastname: Zheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002135:Calcium-Binding Proteins; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D004249:DNA Damage; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D061986:MCF-7 Cells; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger / Q000378:metabolism; D043823:Taxoids / Q000494:pharmacology*; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D002135:Calcium-Binding Proteins; C424126:DLL4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D043823:Taxoids; D000077143:Docetaxel; D053148:Caspase 3; D053179:Caspase 7
keywords: DLL4; MCF-7 cells; Notch1; chemoresistance; docetaxel