RU486 increases radiosensitivity and restores apoptosis through modulation of HPV E6/E7 in dexamethasone-treated cervical carcinoma cells

Merideth C. Kamradt, Najeeb Mohideen, Andrew T M Vaughan

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Objective. Cervical carcinoma tumors containing radioresistant cells are associated with decreased local control and survival. Therefore, strategies to increase cell kill during radiotherapy have a clear rationale. It was previously determined that treatment with the corticosteroid dexamethasone increased radioresistance and decreased apoptosis in C4-1 cervical carcinoma cells. The goal of this study was to determine whether hormone antagonists, specifically Mifepristone (RU486), could reverse the effects of dexamethasone on clonogenic survival and apoptosis following γ-irradiation. Methods. Cervical carcinoma cell line C4-1 cells were exposed to 1 μM dexamethasone in the presence or absence of 1 μM Mifepristone (RU486), a hormone antagonist, and irradiation. Cells were analyzed for steroid-dependent HPV E6/E7 mRNA expression (by Northern blot analysis), clonogenic survival, and apoptosis (by Annexin V staining and the DNA fragmentation assay). In addition, p53 protein levels were determined by Western blot analysis. Results. The hormone antagonist RU486 reversed dexamethasone-dependent upregulation of E6/E7 mRNA and restored radiation-induced p53 expression, apoptosis, and clonogenic survival to levels similar to those observed following irradiation alone. Conclusion. RU486 reverses glucocorticoid- dependent upregulation of HPV E6/E7, which corresponds to restoration of p53 expression, and restores radiosensitivity and apoptosis following γ- irradiation. Therefore, it appears that along with radiation, RU486 may be a beneficial agent in the treatment of hormone-reactive cervical tumors. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)177-182
Number of pages6
JournalGynecologic Oncology
Volume77
Issue number1
DOIs
StatePublished - Apr 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

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