title: 2ME2 increase radiation-induced apoptosis of keloid fibroblasts by targeting HIF-1α in vitro.
abstract: BACKGROUND
  Radiation therapy is considered to be a treatment for keloid scarring; however, radioresistance has been shown to be a serious impediment to treatment efficacy. There is therefore a need for the discovery of novel critical molecular targets whose inhibition might enhance the radiotherapeutic response. An elevated level of hypoxia inducible factor (HIF)-1α expression after radiation therapy in keloid fibroblasts has been demonstrated in our recent experiments. Therefore, we suggested there was a possible close relationship between HIF-1α and keloid radioresistance. The current study aimed to investigate whether target HIF-1α may enhance the radiotherapeutic efficacy of keloids.
  
  
  METHODS
  2-methoxyestradiol (2ME2) was applied to inhibit HIF-1α expression, and the treatment results were assessed by cell proliferation, apoptosis and radiosensitivity. A lentivirus-mediated small interfering RNA (siRNA) transduction method was used to block the expression of HIF-1α gene.
  
  
  RESULTS
  Both mRNA and protein levels can be effectively inhibited after the knockdown of HIF-1α, leading to a significant increase of radiation-induced apoptosis in keloid fibroblasts. Our experiment also demonstrated that 2ME2 could effectively inhibit the protein expression of HIF-1α, which significantly increased the late stage of radiation-induced apoptosis of keloid fibroblasts.
  
  
  CONCLUSIONS
  The present study indicates that HIF-1α might serve as a therapeutic target for keloids. Furthermore, suppression of HIF-1α by 2ME2 may be a promising therapeutic adjuvant in radiation therapy for keloids.
authors: Division of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Fei
authors: F
authors: Long
authors: Division of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Loubin
authors: L
authors: Si
authors: Division of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Xiao
authors: X
authors: Long
authors: Division of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Bob
authors: B
authors: Yang
authors: Division of Plastic and Aesthetic Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Xiaojun
authors: X
authors: Wang
authors: Division of Radiation Oncology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors: Fuquan
authors: F
authors: Zhang
mesh_terms: D000077584:2-Methoxyestradiol; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D049109:Cell Proliferation / Q000187:drug effects / Q000528:radiation effects; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology; D005347:Fibroblasts / Q000378:metabolism / Q000528:radiation effects*; D055785:Gene Knockdown Techniques; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D007627:Keloid / Q000473:pathology / Q000532:radiotherapy; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000378:metabolism; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000187:drug effects* / Q000235:genetics; D050257:Tubulin Modulators / Q000494:pharmacology*
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D050257:Tubulin Modulators; D004958:Estradiol; D000077584:2-Methoxyestradiol
keywords: 2-methoxyestradiol; HIF-1α; keloids; radiosensitivity