title: Paclitaxel-doxorubicin sequence is more effective in breast cancer cells with heat shock protein 27 overexpression.
abstract: BACKGROUND
  Cancer cells with overexpression of heat shock protein 27 (HSP27) are resistant to chemotherapeutic drug doxorubicin (Dox). Paclitaxel (Pacl) was reported to suppress HSP27 expression in ovarian and uterine cancer cells. The purposes of this study were to investigate whether Pacl inhibits the expression of HSP27 in breast cancer cells, whether Pacl can sensitize breast cancer cells with HSP27 overexpression to Dox, and to define a more effective schedule for the combination of Dox with Pacl.
  
  
  METHODS
  The HSP27 high-expressing human breast cancer cell lines, MCF-7 and MDA-MB-435, and the HSP27 low-expressing cell line, MDA-MB-231, were used in this study. The level of HSP27, topoisomerase (Topo) IIalpha and beta expression were assessed by Western blotting. The cytotoxic activities of Dox, Pacl and combination of these two drugs were evaluated by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay and flow cytometric assays.
  
  
  RESULTS
  Pacl (0.1 micromol/L) inhibited HSP27 expression by approximately 2-fold in MCF-7 and MDA-MB-435 cells, while up-regulating the level of topo IIalpha and beta. In contrast, expression of HSP27 in MDA-MB-231 did not change significantly following Pacl treatment. There were synergistic effects in both treatment sequences (Pacl-Dox and Dox-Pacl) when Pacl was combined with Dox. Compared with those treated with the Dox-Pacl sequence, the Pacl-Dox sequence had a stronger effect in cancer cells with HSP27 overexpression, as MCF-7 and MDA-MB-435 treated with the Pacl-Dox sequence had lower viabilities and a higher apoptotic rate.
  
  
  CONCLUSIONS
  Paclitaxel significantly decreases the level of HSP27 in breast cancer cells overexpressing HSP27. In combination therapies, the Pacl-Dox sequence is more effective in clearing breast cancer cells with high HSP27 expression compared with the Dox-Pacl sequence.
authors.affiliation: Department of General Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Shi
authors.forename: Ming-ming
authors.initials: MM
authors.lastname: Wang
authors.forename: Li-yu
authors.initials: LY
authors.lastname: Jiang
authors.forename: Huan-tao
authors.initials: HT
authors.lastname: Liu
authors.forename: Jing-zhong
authors.initials: JZ
authors.lastname: Sun
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000737:chemistry / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D055551:HSP27 Heat-Shock Proteins / Q000032:analysis*; D006360:Heat-Shock Proteins; D006801:Humans; D018832:Molecular Chaperones; D017239:Paclitaxel / Q000008:administration & dosage
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D004317:Doxorubicin; D017239:Paclitaxel