title: All-trans retinoic acids induce differentiation and sensitize a radioresistant breast cancer cells to chemotherapy.
abstract: BACKGROUND
  Radiotherapy is of critical importance in the treatment of breast cancer. However, not all patients derive therapeutic benefit and some breast cancers are resistant to the treatment, and are thus evidenced with prospective distant metastatic spread and local recurrence. In this study, we investigated the potential therapeutic effects of all-trans retinoic acid (ATRA) on radiation-resistant breast cancer cells and the associated invasiveness.
  
  
  METHODS
  The MCF7/C6 cells with gained radiation resistance after a long term treatment with fractionated ionizing radiation were derived from human breast cancer MCF7 cell line, and are enriched with cells expressing putative breast cancer stem cell biomarker CD44(+)/CD24(-/low)/ALDH(+). The enhanced invasiveness and the acquired resistances to chemotherapeutic treatments of MCF7/C6 cells were measured, and potential effects of all-trans retinoic acid (ATRA) on the induction of differentiation, invasion and migration, and on the sensitivities to chemotherapies in MCF7/C6 cells were investigated.
  
  
  RESULTS
  MCF7/C6 cells are with enrichment of cancer stem-cell like cells with positive staining of CD44(+)/CD24(-/low), OCT3/4 and NANOG. MCF7/C6 cells showed an increased tumoregensis potential and enhanced aggressiveness of invasion and migration. Treatment with ATRA induces the differentiation in MCF7/C6 cells, resulting in reduced invasiveness and migration, and increased sensitivity to Epirubincin treatment.
  
  
  CONCLUSIONS
  Our study suggests a potential clinic impact for ATRA as a chemotherapeutic agent for treatment of therapy-resistant breast cancer especially for the metastatic lesions. The study also provides a rationale for ATRA as a sensitizer of Epirubincin, a first-line treatment option for breast cancer patients.
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.|Department of Biochemistry, Laboratory of Molecular Biology, Anhui Medical University, Hefei, China.
authors.forename: Yunwen
authors.initials: Y
authors.lastname: Yan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, USA.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, USA.|School of Life Sciences, Anhui University, Hefei, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Xu
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, USA.
authors.forename: Clark
authors.initials: C
authors.lastname: Chen
authors.affiliation: Institute of Clinical Pharmacology, Anhui Medical University, Hefei, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Radiation Oncology, University of California, Davis, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Fan
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, USA.
authors.forename: Xufeng
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Radiation Oncology, University of California, Davis, USA.
authors.forename: Jian Jian
authors.initials: JJ
authors.lastname: Li
authors.affiliation: Department of Biochemistry, Laboratory of Molecular Biology, Anhui Medical University, Hefei, China. wangyuan@ahmu.edu.cn.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pathology and Laboratory Medicine, University of California, Los Angeles, USA.
authors.forename: Jiaoti
authors.initials: J
authors.lastname: Huang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors; D009361:Neoplasm Invasiveness; D014411:Neoplastic Stem Cells / Q000187:drug effects; D011836:Radiation Tolerance / Q000187:drug effects*; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D018960:Hyaluronan Receptors; D014212:Tretinoin
keywords: ATRA; Breast cancer; Cancer stem cell; Radiation resistance