[Experimental study on the mechanism of cisplatin resistance and its reversion in human ovarian cancer].
OBJECTIVE
To explore the mechanism of cisplatin resistance and its reversion in human ovarian cancer.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Liang
Z
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1st Affiliated Hospital, Chongqing Medical University.
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D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002945:Cisplatin / Q000494:pharmacology*; D018284:Cystadenocarcinoma, Serous / Q000473:pathology*; D018736:DNA Adducts; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D009675:Novobiocin / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000473:pathology*; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D018736:DNA Adducts; D009675:Novobiocin; D000666:Amphotericin B; D002945:Cisplatin