Synergistic effects of ICI 182,780 on the cytotoxicity of cisplatin in cervical carcinoma cell lines.
OBJECTIVE
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 G(2)/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.
García-López
Patricia
P
División de Investigación Básica, Instituto Nacional de Cancerología. Av. San Fernando # 22, Tlalpan 14000, Apartado Postal 22026 México D.F., Mexico. pgarcia_lopez@yahoo.com.mx
Rodríguez-Dorantes
Mauricio
M
Pérez-Cárdenas
Enrique
E
Cerbón
Marco
M
Mohar-Betancourt
Alejandro
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005562:Formazans / Q000378:metabolism; D000077267:Fulvestrant; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology
D000970:Antineoplastic Agents; D004965:Estrogen Antagonists; D005562:Formazans; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D000077267:Fulvestrant; D004958:Estradiol; C059088:1,5-bis(2-methoxy-4-nitro-5-sulfophenyl)-3-((phenylamino)carbonyl)formazan; D002945:Cisplatin