[Circumvention of cisplatin resistant ovarian cancer cells by antiestrogens].
Antiestrogens (AEs) have been considered to elicit antitumor effects via estrogen receptor. However, recent reports have demonstrated that AEs had an antitumor effect even in cases without estrogen receptor, and that AEs caused various kinds of biological behavior such as a chemosensitizing effect. We therefore investigated the possibility of circumvention of cisplatin (CDDP) resistance due to the chemosensitizing effect of AEs by using 5 ovarian cancer cell lines. They were named KF, MH, KK, KFra and KFrb cell lines. KF and MH were derived from serous cystadenocarcinomas, and KK from a clear cell carcinoma. KFra and KFrb were CDDP-resistant cell lines developed from the KF cell line. MCF-7 cell line derived from breast cancer was used as a control. The study of a 50% inhibitory concentration (IC50) revealed that clomiphene (CLO) had the most potent antiproliferative effect among the AEs used, and was followed by tamoxifen (TAM) and toremifene (TOR) with a similar effect. On the whole, the degree of CDDP sensitivity was not correlated with the degree of AE sensitivity. KFra cell line which had the highest CDDP-resistance among the 5 ovarian cancer cell lines used was the most sensitive to AEs, especially to CLO. In the study on the combined administration of CDDP and AEs, 1 microM of CLO significantly reduced the IC50 of CDDP to KFrb, KK and MCF-7 cell lines. Similarly, 1 microM of TAM significantly reduced the IC50 of CDDP to KF, KFra and MCF-7 cell lines, and 1 microM of TOR significantly reduced it to KFra, KK and MCF-7 cell lines.(ABSTRACT TRUNCATED AT 250 WORDS)
Ishii
K
K
Department of Obstetrics and Gynecology, National Defense Medical College, Saitama.
Kita
T
T
Kudo
K
K
Hisano
A
A
Hirata
J
J
Imaizumi
E
E
Tode
T
T
Kikuchi
Y
Y
Nagata
I
I
D002945:Cisplatin / Q000494:pharmacology*; D002996:Clomiphene / Q000494:pharmacology; D004351:Drug Resistance; D004357:Drug Synergism; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005260:Female; D006801:Humans; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D011493:Protein Kinase C / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D017312:Toremifene / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004965:Estrogen Antagonists; D013629:Tamoxifen; D002996:Clomiphene; D017312:Toremifene; D011493:Protein Kinase C; D002945:Cisplatin