novobiocin and Cystadenocarcinoma--Serous

To explore the mechanism of cisplatin resistance and its reversion in human ovarian cancer.. A xenografted cisplatin resistant mice model of human ovarian cancer, SKOV3/cp, was developed by the microencapsulated technique. The multiple changes of bio-chemical markers in the model were determined, and various modulators for reversion were tested.. Intracellular platinum accumulation in SKOV3 was 5.1 times, Pt-DNA adducts 2.4 times and interstrand cross link of DNA (ISC) 4.8 times of those in cisplatin-resistant cell line, SKOV3/cp. These changes in SKOV3/cp could not be reversed by verapamil. Amphotercin B (AmB) and Novobiocin (NVB) could raise the concentrations of platinum and Pt-DNA adducts in SKOV3/cp, resulting in complete or partial reversion of cisplatin-resistance of SKOV3/cp. There were no differences in total glutathione (GSH) level and in sensitivity to CdCl2 between SKOV3 and SKOV3/cp.. It is suggested that the primary factor causing SKOV3/cp resistance to cisplatin is the reduction of intracellular platinum accumulation and the augmentation of the ability to remove Pt-DNA adducts. The resistance is not considered to be associated with the multidrug resistant, GSH, metallothionein systems. AmB and NVB can overcome cisplatin resistance of SKOV3/cp in vitro and in vivo.

Topics: Amphotericin B; Animals; Antineoplastic Agents; Cisplatin; Cystadenocarcinoma, Serous; DNA Adducts; Drug Resistance, Neoplasm; Female; Humans; Mice; Mice, Inbred BALB C; Neoplasm Transplantation; Novobiocin; Ovarian Neoplasms; Tumor Cells, Cultured