title: Antihormonal agents as a strategy to improve the effect of chemo-radiation in cervical cancer: in vitro and in vivo study.
abstract: BACKGROUND
  Over the past few years, the concurrent use of cisplatin-based chemotherapy and radiation therapy has dramatically improved the local response and increased overall survival in early-stage cervical cancer. However, for the advanced stages of the disease this standard treatment has proved insufficient. We investigated the capacity of Mifepristone and ICI 182,780, which are anti-progestin and anti-estrogen drugs, respectively, to act as chemo-radiosensitizing agents in cervical cancer cells and cervix xenografts.
  
  
  METHODS
  The effect of chemo-radiation alone or combined with Mifepristone or ICI 182,780 was evaluated in HeLa cells and with tumor growth in cervix xenografts. After concomitant chemo-radiotherapy, the effect of each of these antihormonal agents on apoptosis (determined by Annexing V assay) and the cell cycle phases were determined by flow cytometry. The expression of angiogenic factor VEGF in tumor samples was determined using quantitative RT-PCR analysis of VEGF gene expression.
  
  
  RESULTS
  Compared to radiation alone or radiation/cisplatin therapy, there was significantly higher cytotoxicity and a greater antitumoral effect with the combined application of radiation/cisplatin and Mifepristone or ICI 182,780. Analyses of the apoptosis and cell cycle demonstrated changes only with ICI, not with Mifepristone, when was applied in combination with radiation/cisplatin. The analysis of VEGF mRNA expression levels in tumors at the end of the study demonstrated a significant inhibition, compared to radiation only or the radiation/cisplatin treatment, after concurrent chemo-radiotherapy and each one of the antihormonal drugs.
  
  
  CONCLUSIONS
  Mifepristone and ICI 182,780 may be potentially promising chemo-radiosensitizing compounds to be used in combination with ionizing irradiation and cisplatin in the treatment of patients with advanced cervical cancer.
authors.affiliation: Instituto Nacional de Cancerología, Subdirección de Investigación Básica, México D.F., 14080, México. monaco445@yahoo.com.mx.|Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, México D.F., 04510, México. monaco445@yahoo.com.mx.
authors.forename: Mariana
authors.initials: M
authors.lastname: Segovia-Mendoza
authors.affiliation: Instituto Nacional de Cancerología, Subdirección de Investigación Básica, México D.F., 14080, México. fcojl@yahoo.com.
authors.forename: Rafael
authors.initials: R
authors.lastname: Jurado
authors.affiliation: Instituto Nacional de Cancerología, Subdirección de Investigación Básica, México D.F., 14080, México. rosermir83@gmail.com.|Instituto de Física, Universidad Nacional Autónoma de México, México D.F., 04510, México. rosermir83@gmail.com.
authors.forename: Roser
authors.initials: R
authors.lastname: Mir
authors.affiliation: Instituto de Física, Universidad Nacional Autónoma de México, México D.F., 04510, México. medina@fisica.unam.mx.|Unidad de Investigación Biomédica en Cáncer INCan-UNAM, Instituto Nacional de Cancerología, México D.F., 14080, México. medina@fisica.unam.mx.
authors.forename: Luis A
authors.initials: LA
authors.lastname: Medina
authors.affiliation: Instituto Nacional de Enfermedades Respiratorias, Departamento de Enfermedades Crónico-Degenerativas, México D.F, Mexico. hpradog@yahoo.com.
authors.forename: Heriberto
authors.initials: H
authors.lastname: Prado-Garcia
authors.affiliation: Instituto Nacional de Cancerología, Subdirección de Investigación Básica, México D.F., 14080, México. pgarcia_lopez@yahoo.com.mx.
authors.forename: Patricia
authors.initials: P
authors.lastname: Garcia-Lopez
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D011839:Radiation, Ionizing; D047368:Tumor Burden / Q000187:drug effects / Q000528:radiation effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000532:radiotherapy; D042442:Vascular Endothelial Growth Factors / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D018931:Antineoplastic Agents, Hormonal; D042442:Vascular Endothelial Growth Factors; D002945:Cisplatin