Establishment and characterization of an acquired cisplatin-resistant subline in a human osteosarcoma cell line.
A cisplatin (CDDP)-resistant human osteosarcoma cell line (OST/R) was established by continuous exposure to CDDP. OST/R cells proved to be 6.73 times more resistant to CDDP compared with parental OST cells, and showed cross-resistance to carboplatin (CBDCA). The mechanism of CDDP resistance was a significant decrease of intracellular platinum accumulation which was 40% of that in OST cells. OST/R cells were exposed to CDDP for 6 hours, the platinum was released from the cytoplasm of OST/R cells without reaching a state of equilibrium. DNA synthesis in OST/R cells was not inhibited by CDDP exposure, while in OST cells it was reduced by 50%. These data provide the first evidence that the increased efflux of platinum may play an important role in CDDP-resistance.
Department of Orthopedic Surgery, School of Medicine, Kanazawa University, Ishikawa, Japan.
N
N
Asada
H
H
Tsuchiya
Y
Y
Ueda
K
K
Tomita
D000970:Antineoplastic Agents / Q000633:toxicity*; D001692:Biological Transport; D001859:Bone Neoplasms; D016190:Carboplatin / Q000493:pharmacokinetics / Q000633:toxicity*; D002460:Cell Line; D002945:Cisplatin / Q000493:pharmacokinetics* / Q000633:toxicity*; D003593:Cytoplasm / Q000378:metabolism; D004273:DNA, Neoplasm / Q000096:biosynthesis; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007700:Kinetics; D012516:Osteosarcoma; D010984:Platinum / Q000378:metabolism; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004273:DNA, Neoplasm; D010984:Platinum; D016190:Carboplatin; D002945:Cisplatin