Possible mechanisms of resistance to cis-diamminedichloroplatinum (II) of human ovarian cancer cells

Japanese Journal of Cancer Research : Gann
Y KikuchiI Nagata

Abstract

The mechanism of cis-diamminedichloroplatinum (II) (CDDP) resistance was examined by using a CDDP-resistant (KFr) cell line established by continuous exposure of KF cells (derived from serous cystadenocarcinoma of the ovary) to escalating doses of CDDP. When KFr cells were incubated with 66.7 microM CDDP, the uptake of CDDP was significantly inhibited and the cellular content in the KFr cells was about a half of that in KF cells after incubation for 4 h. When the KF or KFr cells were incubated for 4 h with 100 microM CDDP, the release pattern of CDDP from KFr cells was similar to that from KF cells. In addition, the DNA histogram of both KF and KFr cells revealed that KF cells seemed to contain two clones of cell population and the KFr cells may have been selected by exposure to CDDP. At 3 h after intraperitoneal administration of 0.5 mg of CDDP per mouse to nude mice with KF or KFr tumor, the CDDP content in the KFr tumor was significantly lower than that in the KF tumor. In contrast, at 6 or 9 h after CDDP administration the CDDP content in the KFr tumor was significantly higher than that in the KF tumor. Furthermore, the KFr cells had cross-resistance to various CDDP analogues including carboplatin. It was shown that cellula...Continue Reading

References

May 1, 1988·Japanese Journal of Cancer Research : Gann·Y KikuchiY Tenjin
Aug 1, 1986·British Journal of Cancer·H Eichholtz-Wirth, B Hietel
Apr 1, 1985·Proceedings of the National Academy of Sciences of the United States of America·E FreiW A Haseltine
May 1, 1984·Annals of Internal Medicine·P J Loehrer, L H Einhorn
Aug 30, 1984·Biochemical and Biophysical Research Communications·Y KikuchiK Kato
Dec 1, 1982·Cellular Immunology·A Yen, D G Fairchild

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