Asada N, Tsuchiya H, Ueda Y, Tomita K
Department of Orthopedic Surgery, School of Medicine, Kanazawa University, Ishikawa, Japan.
Anticancer Res. 1998 May-Jun;18(3A):1765-8.
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.
通过持续暴露于顺铂（CDDP）建立了一种顺铂耐药的人骨肉瘤细胞系（OST/R）。与亲代OST细胞相比，OST/R细胞对顺铂的耐药性高6.73倍，并对卡铂（CBDCA）表现出交叉耐药性。顺铂耐药的机制是细胞内铂积累显著减少，仅为OST细胞的40%。将OST/R细胞暴露于顺铂6小时，铂从OST/R细胞的细胞质中释放出来，未达到平衡状态。顺铂暴露并未抑制OST/R细胞中的DNA合成，而在OST细胞中DNA合成减少了50%。这些数据首次证明铂外流增加可能在顺铂耐药中起重要作用。
