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[Establishment of adriamycin-resistant human ovarian carcinoma cell line and its mechanism of multidrug resistance].

Li Py, C Lin

Abstract

A multidrug-resistant cell line (A2780/ADM) of human ovarian carcinoma which can resist 0.8 microgram.ml-1 of adriamycin (ADM) was obtained by step-wise selection exposure to increasing doses of ADM. A2780/ADM cells showed 17-fold higher resistance to ADM than A2780 cells. The doubling times were 43.8 h in A2780/ADM and 26.3 h in A2780 cells. Colony formation rates were 15%-20% in A2780/ADM and 65%-75% in A2780 cells. A2780/ADM cell line was also shown to significantly cross-resistant to vincristine (VCR) and VP-16, but no cross-resistance was found to 5-Fu, PDD or Mel. A further investigation showed that intracellular accumulation of ADM in A2780/ADM was significantly decreased. Expressions of P-glycoprotein and GST-pi were increased in A2780/ADM by means of immunohistochemical method. Verapamil (Ver) combined with ADM was found to increase the sensitivity and reverse the resistance to ADM in A2780/ADM. This study indicates that A2780 ADM has the peculiarity of multidrug resistance and there may be other mechanism of drug-resistance besides MDR related to P-170.

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Key concepts: Multiple drug resistance, P-glycoprotein, Cell culture, Intracellular, Chemistry, Verapamil, Vincristine, Drug resistance