title: Establishment of paclitaxel-resistant breast cancer cell line and nude mice models, and underlying multidrug resistance mechanisms in vitro and in vivo.
abstract: BACKGROUND
  Breast cancer is a common malignant tumor which affects health of women and multidrug resistance (MDR) is one of the main factors leading to failure of chemotherapy. This study was conducted to establish paclitaxel-resistant breast cancer cell line and nude mice models to explore underlying mechanisms of MDR.
  
  
  METHODS
  The breast cancer drug-sensitive cell line MCF-7 (MCF-7/S) was exposed in stepwise escalating paclitaxel (TAX) to induce a resistant cell line MCF-7/TAX. Cell sensitivity to drugs and growth curves were measured by MTT assay. Changes of cell morphology and ultrastructure were examined by optical and electron microscopy. The cell cycle distribution was determined by flow cytometry. Furthermore, expression of proteins related to breast cancer occurrence and MDR was tested by immunocytochemistry. In Vivo, nude mice were injected with MCF-7/S and MCF-7/TAX cells and weights and tumor sizes were observed after paclitaxel treatment. In addition, proteins involved breast cancer and MDR were detected by immunohistochemistry.
  
  
  RESULTS
  Compared to MCF-7/S, MCF-7/TAX cells had a higher resistance to paclitaxel, cross-resistance and prolonged doubling time. Moreover, MCF-7/TAX showed obvious alterations of ultrastructure. Estrogen receptor (ER) expression was low in drug resistant cells and tumors while expression of human epidermal growth factor receptor 2 (HER2) and Ki-67 was up-regulated. P-glycoprotein (P-gp), lung resistance-related protein (LRP) and glutathione-S-transferase-π (GST-π) involved in the MDR phenotype of resistant cells and tumors were all overexpressed.
  
  
  CONCLUSIONS
  The underlying MDR mechanism of breast cancer may involve increased expression of P-gp, LRP and GST-π.
authors.affiliation: Department of Pharmacy, the First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, Shaanxi, China E-mail : dongyalin@mail.xjtu.edu.cn.
authors.forename: Si-Ying
authors.initials: SY
authors.lastname: Chen
authors.forename: Sa-Sa
authors.initials: SS
authors.lastname: Hu
authors.forename: Qian
authors.initials: Q
authors.lastname: Dong
authors.forename: Jiang-Xia
authors.initials: JX
authors.lastname: Cai
authors.forename: Wei-Peng
authors.initials: WP
authors.lastname: Zhang
authors.forename: Jin-Yao
authors.initials: JY
authors.lastname: Sun
authors.forename: Tao-Tao
authors.initials: TT
authors.lastname: Wang
authors.forename: Jiao
authors.initials: J
authors.lastname: Xie
authors.forename: Hai-Rong
authors.initials: HR
authors.lastname: He
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Xing
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Ya-Lin
authors.initials: YL
authors.lastname: Dong
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018929:Cell Culture Techniques; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017239:Paclitaxel / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel