Sekiya S, Oosaki T, Andoh S, Suzuki N, Nagao K, Takamizawa H
Department of Obstetrics and Gynecology, Chiba University School of Medicine, Japan.
Eur J Cancer Clin Oncol. 1988 May;24(5):851-9. doi: 10.1016/0277-5379(88)90193-9.
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.
通过在体外持续将顺铂敏感的亲本细胞系（ROT68/C1）暴露于递增剂量的药物后，建立了一种对顺铂具有约20倍抗性的大鼠卵巢癌细胞亚系（Cis-Ptr）。ROT68/C1细胞和Cis-Ptr细胞在同源（Sprague-Dawley品系）新生大鼠中均具有致瘤性，并且仅接种Cis-Ptr细胞所形成的肿瘤在体内表现出对顺铂的抗性。对顺铂的抗性伴随着未分化腺癌细胞的表型变化，包括细胞和细胞核增大以及在体外和体内的生长速率减慢。与ROT68/C1细胞相比，Cis-Ptr细胞在暴露于顺铂后显示出DNA合成活性的早期恢复。Cis-Ptr细胞仅对顺铂类似物卡铂存在交叉抗性。这些结果表明，我们的顺铂抗性大鼠卵巢癌细胞可用于研究顺铂抗性的特征和机制。
