title: Increasing the cytotoxicity of doxorubicin in breast cancer MCF-7 cells with multidrug resistance using a mesoporous silica nanoparticle drug delivery system.
abstract: Resistance to cytotoxic chemotherapy is the main cause of therapeutic failure and death in women with breast cancer. Overexpression of various members of the superfamily of adenosine triphosphate binding cassette (ABC)-transporters has been shown to be associated with multidrug resistance (MDR) phenotype in breast cancer cells. MDR1 protein promotes the intracellular efflux of drugs. A novel approach to address cancer drug resistance is to take advantage of the ability of nanocarriers to sidestep drug resistance mechanisms by endosomal delivery of chemotherapeutic agents. Doxorubicin (DOX) is an anthracycline antibiotic commonly used in breast cancer chemotherapy and a substrate for ABC-mediated drug efflux. In the present study, we developed breast cancer MCF-7 cells with overexpression of MDR1 and designed mesoporous silica nanoparticles (MSNs) which were used as a drug delivery system. We tested the efficacy of DOX in the breast cancer cell line MCF-7/MDR1 and in a MCF-7/MDR1 xenograft nude mouse model using the MSNs drug delivery system. Our data show that drug resistance in the human breast cancer cell line MCF-7/MDR1 can be overcome by treatment with DOX encapsulated within mesoporous silica nanoparticles.
authors.affiliation: Department of Radiology, Jinling Hospital, Nanjing University School of Medicine Nanjing, 210002, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Radiology, Jinling Hospital, Nanjing University School of Medicine Nanjing, 210002, China.
authors.forename: Zhaogang
authors.initials: Z
authors.lastname: Teng
authors.affiliation: Department of Pathology, Jinling Hospital, Nanjing University School of Medicine Nanjing, 210002, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Radiology, Jinling Hospital, Nanjing University School of Medicine Nanjing, 210002, China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Radiology, Jinling Hospital, Nanjing University School of Medicine Nanjing, 210002, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Radiology, Jinling Hospital, Nanjing University School of Medicine Nanjing, 210002, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Department of Radiology, Jinling Hospital, Nanjing University School of Medicine Nanjing, 210002, China.
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Radiology, Jinling Hospital, Nanjing University School of Medicine Nanjing, 210002, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Pathology, Jinling Hospital, Nanjing University School of Medicine Nanjing, 210002, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pathology, Jinling Hospital, Nanjing University School of Medicine Nanjing, 210002, China.
authors.forename: Jiandong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Radiology, Jinling Hospital, Nanjing University School of Medicine Nanjing, 210002, China.
authors.forename: Guangming
authors.initials: G
authors.lastname: Lu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics / Q000378:metabolism; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016503:Drug Delivery Systems / Q000379:methods*; D018432:Drug Resistance, Multiple; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053758:Nanoparticles; D012822:Silicon Dioxide; D015854:Up-Regulation / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D012822:Silicon Dioxide; D004317:Doxorubicin
keywords: Breast cancer; MDR; MSNs; drug delivery system