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.