Background: Over the past few years, the concurrent use of cisplatin-based chemotherapy and radiation therapy\nhas dramatically improved the local response and increased overall survival in early-stage cervical cancer. However,\nfor the advanced stages of the disease this standard treatment has proved insufficient. We investigated the capacity\nof Mifepristone and ICI 182,780, which are anti-progestin and anti-estrogen drugs, respectively, to act as chemoradiosensitizing\nagents in cervical cancer cells and cervix xenografts.\nMethods: The effect of chemo-radiation alone or combined with Mifepristone or ICI 182,780 was evaluated in HeLa\ncells and with tumor growth in cervix xenografts. After concomitant chemo-radiotherapy, the effect of each of these\nantihormonal agents on apoptosis (determined by Annexing V assay) and the cell cycle phases were determined by\nflow cytometry. The expression of angiogenic factor VEGF in tumor samples was determined using quantitative\nRT-PCR analysis of VEGF gene expression.\nResults: Compared to radiation alone or radiation/cisplatin therapy, there was significantly higher cytotoxicity and a\ngreater antitumoral effect with the combined application of radiation/cisplatin and Mifepristone or ICI 182,780.\nAnalyses of the apoptosis and cell cycle demonstrated changes only with ICI, not with Mifepristone, when was\napplied in combination with radiation/cisplatin. The analysis of VEGF mRNA expression levels in tumors at the end\nof the study demonstrated a significant inhibition, compared to radiation only or the radiation/cisplatin treatment,\nafter concurrent chemo-radiotherapy and each one of the antihormonal drugs.\nConclusion: Mifepristone and ICI 182,780 may be potentially promising chemo-radiosensitizing compounds to be\nused in combination with ionizing irradiation and cisplatin in the treatment of patients with advanced cervical cancer.
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