title: Anti-tumor activity of folate targeted biodegradable polymer-paclitaxel conjugate micelles on EMT-6 breast cancer model.
abstract: BACKGROUND
  Paclitaxel (PTX) is a first line chemotherapy drug for breast cancer. There have been few studies reported concerning the therapeutic efficacy of paclitaxel-conjugated polymeric micelles in breast cancer in vivo.
  
  
  METHODS
  Two kinds of PTX conjugate micelles, one of which (M(PTX)) contained 25 wt.% of PTX and the other (M(FA/PTX)) contained 22.5 wt.% of PTX and 1.4 wt.% of folate (FA), were prepared for cell apoptosis and anti-tumor activity evaluation on EMT-6 mice breast cancer models in comparison with 0.9 wt.% saline (control) and equivalent PTX. Cell apoptosis was analyzed by flow cytometry. Breast tumors were examined histologically with H&E staining and immunohistochemically by examining Bax and Bcl-2 expression. The survival status of tumor-bearing mice with different treatments was also examined.
  
  
  RESULTS
  On day 5 of the drug administration, the average tumor masses were 0.49, 0.33, 0.22, and 0.18 g for the control, PTX, M(PTX) and M(FA/PTX) groups, respectively. The inhibition rates of tumor growth calculated for the three drug groups were 32.6%, 51.6% and 62.3%, respectively. The percentage of cell apoptosis based on flow cytometry was 1.0%, 36.6%, 55.9% and 66.1%, respectively, which showed statistically significant differences (p<0.05) between three drug groups and the control group. Bcl-2 expression of PTX and M(FA/PTX) groups was lower than control group (p<0.05). Bax expression of drug groups was higher than control group (p<0.05). At an equivalent paclitaxel dose of 26.7 mg/kg, the average survival time was 33 days, 31 days, 34 days and 42 days, respectively (p<0.05).
  
  
  CONCLUSIONS
  The M(FA/PTX) have better anti-tumor activity and are promising in treatment of human breast cancers.
authors.affiliation: Department of Breast Surgery, First Hospital of Jilin University, Changchun 130021, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors.forename: Yonghui
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Breast Surgery, First Hospital of Jilin University, Changchun 130021, China. Electronic address: fanzhimn@163.com.
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Polymer Physics and Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun 130022, China. Electronic address: xbjing@ciac.jl.cn.
authors.forename: Xiabin
authors.initials: X
authors.lastname: Jing
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D005492:Folic Acid / Q000737:chemistry*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008823:Micelles; D017239:Paclitaxel / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D011092:Polyethylene Glycols / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D008823:Micelles; D011092:Polyethylene Glycols; D005492:Folic Acid; D017239:Paclitaxel
keywords: Breast cancer; Drug targeting; Folic acid; Paclitaxel; Polymer–drug conjugate