The isolation and characterization of cisplatin-resistant rat ovarian cancer cells.
A rat ovarian cancer cell subline (Cis-Ptr), which became approximately 20-fold resistant to cisplatin, was developed after continuous exposure of the cisplatin-sensitive parent cell line (ROT68/C1) to increasing doses of the drug in vitro. Both the ROT68/C1 and Cis-Ptr cells were tumorigenic in isologous (Sprague-Dawley strain) newborn rats and only the tumors developed by inoculation of Cis-Ptr cells showed resistance to cisplatin in vivo. Resistance towards cisplatin was accompanied by phenotypic changes of the undifferentiated adenocarcinoma cells including enlargement of the cell and nucleus and a slower growth rate both in vitro and in vivo. Compared to the ROT68/C1 cells, the Cis-Ptr showed an early recovery of DNA synthetic activity after exposure to cisplatin. Cross-resistance of the Cis-Ptr cells was found only to a cisplatin analog, carboplatin. These results suggest that our cisplatin resistant rat ovarian cancer cells are useful in the investigation of the characteristics and mechanisms of cisplatin resistance.
Sekiya
S
S
Department of Obstetrics and Gynecology, Chiba University School of Medicine, Japan.
Oosaki
T
T
Andoh
S
S
Suzuki
N
N
Nagao
K
K
Takamizawa
H
H
D000230:Adenocarcinoma / Q000188:drug therapy / Q000473:pathology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000627:therapeutic use*; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004351:Drug Resistance; D005260:Female; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D014407:Tumor Cells, Cultured / Q000187:drug effects
D004273:DNA, Neoplasm; D002945:Cisplatin