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 cisplatin resistant cell subline of SKOV3, SKOV3/cp, was established, and a xenograft mice model of human ovarian cancer was established by microencapsulation technology. Various biochemical changes and the effects of modulators on the resistance in the model were observed.


RESULTS
The intracellular platinum accumulation. Pt-DNA adducts and interstrand cross links of DNA (ISC) in SKOV3 was 5.1, 2.4 and 4.8 times respectively of those in SKOV3/cp cell line. Amphotericin B (AmB) and Novobiocin (NVB) could raise platinum accumulation and Pt-DNA adducts concentration in SKOV3/cp and this resulted in reversion of cisplatin resistance.


CONCLUSIONS
The primary factors resulting in SKOV3/cp resistance to cisplatin are the reduction of intracellular drugs and the augmentation of the ability to remove Pt-DNA adducts. AmB and NVB can reverse cisplatin resistance in SKOV3/cp cells.
Liang
Z
Z
Department of Obstetrics and Gynecology, Memorial Hospital, Sun Yat-Sen University of Medical Sciences, Guangzhou.
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D000230:Adenocarcinoma / Q000473:pathology*; D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D018736:DNA Adducts / Q000187:drug effects; 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 / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D018736:DNA Adducts; D009675:Novobiocin; D000666:Amphotericin B; D002945:Cisplatin