RU486 Increases Radiosensitivity and Restores Apoptosis through Modulation of HPV E6/E7 in Dexamethasone-Treated Cervical Carcinoma Cells

Authors: Kamradt M.C.^{1, 2}; Mohideen N.²; Vaughan A.T.M.²

Source: Gynecologic Oncology, Volume 77, Number 1, April 2000 , pp. 177-182(6)

Publisher: Academic Press

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 -irradiation.

Methods. Cervical carcinoma cell line C4-1 cells were exposed to 1 M dexamethasone in the presence or absence of 1 M 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 -irradiation. Therefore, it appears that along with radiation, RU486 may be a beneficial agent in the treatment of hormone-reactive cervical tumors. Copyright 2000 Academic Press.

Language: English

Document Type: Research article

Affiliations: 1: Department of Cell Biology, Neurobiology and Anatomy 2: Department of Cell Biology, Neurobiology and Anatomy, Department of Radiation Oncology, Loyola University Medical Center, Maywood, Illinois, 60153

Publication date: 2000-04-01

• In this: publication
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• In this Subject: Obstetrics & Gynecology ,  Oncology
• By this author: Kamradt M.C. ;  Mohideen N. ;  Vaughan A.T.M.

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