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Synergistic effects of ICI 182,780 on the cytotoxicity of cisplatin in cervical carcinoma cell lines

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Abstract

Purpose

We investigated the ability of the novel pure antiestrogen ICI 182,780 to modulate the cytotoxic effects of cisplatin in several cervical cancer cell lines.

Methods

The effect of cisplatin alone and cisplatin combined with ICI 182,780 on cellular death was studied using an assay based on a tetrazolium dye (sodium 3′-[1-(phenylamino-carbonyl)-3,4-tetrazolium], XTT). Before and after treatment with ICI 182,780, expression of the estrogen and progesterone receptor genes were assessed by a reverse transcriptase polymerase chain reaction (RT-PCR). Cell-cycle modifications after combined treatment with cisplatin and ICI 182,780 were studied by flow cytometry.

Results

Analysis of the data by the isobologram method showed that the combination of ICI 182,780 and cisplatin produced a synergistic antiproliferative effect in cervical cancer cells. The effect of ICI 182,780 on the cytotoxicity of cisplatin could be mediated, at least partially, by inhibition of estrogen and progesterone gene expression and by arresting the cell cycle at the G2/M phase.

Conclusions

Our results suggest that ICI 182,780 can improve the efficacy of cisplatin in cancer cells and that this antihormonal drug therapy may be a useful candidate for further evaluation in combination with antineoplastic drugs, particularly cisplatin, in the treatment of cancer.

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Acknowledgements

The authors would like to thank Dr. Alfonso Dueñas for his valuable comments concerning this work and Ms. Teresa Cadena for technical assistance. This project was support by CONACYT (México) grant I35551-M.

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Authors and Affiliations

  1. División de Investigación Básica, Instituto Nacional de Cancerología. Av. San Fernando # 22, Tlalpan 14000, Apartado Postal 22026, México D.F., Mexico

    Patricia García-López, Enrique Pérez-Cárdenas & Alejandro Mohar-Betancourt

  2. Instituto de Investigaciones Biomédicas, Universidad Nacional Autonoma de Mexico, C.P. 04510, México D.F., Mexico

    Alejandro Mohar-Betancourt

  3. Facultad de Química, Universidad Nacional Autonoma de Mexico, C.P. 04510, México D.F., Mexico

    Mauricio Rodríguez-Dorantes & Marco Cerbón

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  1. Patricia García-López
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  2. Mauricio Rodríguez-Dorantes
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  3. Enrique Pérez-Cárdenas
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  5. Alejandro Mohar-Betancourt
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Correspondence to Patricia García-López.

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García-López, P., Rodríguez-Dorantes, M., Pérez-Cárdenas, E. et al. Synergistic effects of ICI 182,780 on the cytotoxicity of cisplatin in cervical carcinoma cell lines. Cancer Chemother Pharmacol 53, 533–540 (2004). https://doi.org/10.1007/s00280-003-0760-3

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  • DOI: https://doi.org/10.1007/s00280-003-0760-3

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