Open AccessPossible Mechanisms of Resistance to cis ‐Diamminedichloroplatinum (II) of Human Ovarian Cancer Cells
Author(s) -
Kikuchi Yoshihiro,
Iwano Ichiro,
Miyauchi Munenori,
Kita Tsunekazu,
Sugita Michio,
Tenjin Yoshio,
Nagata Ichiro
Publication year - 1990
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1990.tb02630.x
Subject(s) - ovarian cancer , cancer research , medicine , cancer , oncology , resistance (ecology) , biology , endocrinology , ecology
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 μ M 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 μ M 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 cellular uptakes of two CDDP analogues into KFr cells were significantly lower than those into KF cells.