title: AKR1C3 overexpression mediates methotrexate resistance in choriocarcinoma cells.
abstract: BACKGROUND
  Chemotherapy is typically used to treat choriocarcinoma, but a small proportion of tumors develop resistance to chemotherapy. Similarly, methotrexate (MTX) is a first-line chemotherapy used to treat choriocarcinoma; although ~30% of patients are drug-resistant for MTX mono-therapy. Thus, we sought to elucidate the mechanism of chemotherapeutic-resistance of MTX.
  
  
  METHODS
  RNA interference technology, colony formation, and MTT assays were used to investigate the role of aldo-keto reductase family 1, member C3 (AKR1C3) in MTX resistance in choriocarcinoma cells.
  
  
  RESULTS
  AKR1C3 expression was higher in JeG-3R cells compared to JeG-3 cells and targeted inhibition of AKR1C3 expression with shRNA suppresses growth of choriocarcinoma cells as measured by colony formation and MTT assays. Overexpression of AKR1C3 increased chemotherapeutic resistance in JeG-3 cells. Furthermore, AKR1C3 silencing increases sensitivity to MTX in JeG-3R choriocarcinoma cells. Increasing MTX sensitivity spears to be related to DNA damage induction by increased reactive oxygen species (ROS), apoptosis, and cell cycle arrest.
  
  
  CONCLUSIONS
  Data show that AKR1C3 is critical to the development of methotrexate resistance in choriocarcinoma and suggest that AKR1C3 may potentially serve as a therapeutic marker for this disease.
authors.affiliation: 1. Departments of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.affiliation: 1. Departments of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xiang
authors.affiliation: 1. Departments of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Changji
authors.initials: C
authors.lastname: Xiao
authors.affiliation: 1. Departments of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guo
authors.affiliation: 1. Departments of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: 1. Departments of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 2. Reproductive Health Centre, National Science Institute for Family Planning, Beijing, People's Republic of China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Shen
mesh_terms: D015096:3-Hydroxysteroid Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D000074425:Aldo-Keto Reductase Family 1 Member C3; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002822:Choriocarcinoma / Q000235:genetics / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000235:genetics* / Q000502:physiology*; D005434:Flow Cytometry; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000235:genetics / Q000378:metabolism*; D008727:Methotrexate / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D015096:3-Hydroxysteroid Dehydrogenases; D006911:Hydroxyprostaglandin Dehydrogenases; C487341:AKR1C3 protein, human; D000074425:Aldo-Keto Reductase Family 1 Member C3; D008727:Methotrexate
keywords: AKR1C3; Chemotherapeutic-resistance.; Choriocarcinoma cells; Methotrexate (MTX); ROS