Discrepancy of uterine leiomyoma and myometrium to hypoxia-induced endoplasmic reticulum stress after uterine occlusion therapy accounts for therapeutic effect

Arch Gynecol Obstet. 2014 May;289(5):1039-45. doi: 10.1007/s00404-013-3100-9. Epub 2013 Nov 28.

Abstract

Purpose: Uterine artery occlusion (UAO) is a promising method for the treatment of leiomyoma. This study is intended to demonstrate the discrepancy of ER stress-induced apoptosis in leiomyoma and myometrium as a result of UAO therapy.

Methods: Primary cultured leiomyoma and myometrial cells were incubated in low oxygen supply (1 % O2). Then, real time RT-PCR and Western blotting were performed to analyze the mRNA and protein levels of ER stress-related molecules including GRP78, CHOP, JNK, Bax, Bcl-2 and Caspase4. Furthermore, the activity of Caspase4 was detected. Tissues of leiomyoma and myometria were also collected before and 30 min after UAO during surgery and evaluated.

Results: The leiomyoma cells and tissues expressed higher ER stress-related molecules compared to myometrial cells or tissues, while the levels of Bcl-2, an anti-apoptotic protein, declined. In myometrial cells, an elevated level of Caspase4 activation as well as its expression was not significant during the first 12 h, suggesting that hypoxia might not intensely affect the myometrium compared with leiomyoma.

Conclusion: ER stress-related apoptosis partly accounts for the effects of UAO therapy on uterine leiomyoma, which leads to the death of leiomyoma while maintaining the survival of the uterus itself.

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / physiology
  • Blotting, Western
  • Endoplasmic Reticulum Chaperone BiP
  • Endoplasmic Reticulum Stress / genetics
  • Endoplasmic Reticulum Stress / physiology*
  • Female
  • Genes, bcl-2 / genetics
  • Humans
  • Hypoxia / etiology
  • Hypoxia / metabolism
  • Leiomyoma / genetics
  • Leiomyoma / metabolism*
  • Leiomyoma / pathology
  • Leiomyoma / surgery
  • Myometrium / cytology
  • Myometrium / metabolism*
  • RNA, Messenger / genetics
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction
  • Transcription, Genetic / drug effects
  • Tumor Cells, Cultured
  • Uterine Neoplasms / metabolism*
  • Uterine Neoplasms / pathology
  • Uterine Neoplasms / surgery

Substances

  • Endoplasmic Reticulum Chaperone BiP
  • HSPA5 protein, human
  • RNA, Messenger