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Zhonghua Zhong Liu Za Zhi. 2001 Jul;23(4):305-8.

[Comparison of stepwise and pulse induced cisplatin-resistant ovarian cancer cell sublines].

[Article in Chinese]

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  • 1Department of Obstetrics and Gynecology, Chinese PLA General Hospital, Chinese Academy of Military Sciences, Beijing 100853, China.



To investigate the mechanism responsible for acquired cisplatin resistance induced in human ovarian cancer cell lines by different methods.


Two resistant cell lines, Skov3/CDDP-P and Skov3/CDDP-50, were established by pulse or stepwise exposures of ovarian cancer cell line Skov3 to cisplatin (CDDP) for 10-12 months with the drug sensitivity monitored by MTT test. The growth rate and cell cycle were compared. The intracellular drug concentration was measured by FACS after 1 hour incubation in 20 mumol/L ADM. The drug-resistance-associated genes: MDR1, MRP, LRP and GST-pi were monitored by RT-PCR and western blotting.


The resistance indexes (RI) of Skov3/CDDP-P and Skov3/CDDP-50 were 3.7 and 48.6 to cisplatin, 4.0 and 33.0 to Taxol, 2.2 and 7.3 to adriamycin, 1.5 and 3.4 to VP16, and the intracellular ADM concentration was lowered by 34.6% and 47.2% respectively. Both resistant cell lines grew slowly and exhibited changes in morphology and cell cycle. The expression of the resistance-associated genes MDR1, MRP and LRP was enhanced in both resistant cell lines. However, Skov3/CDDP-50 showed greater increase in MDR1 but Skov3/CDDP-P showed more in MRP. There were no significant changes in GST-pi expression either at mRNA or protein level. The TOPO II activity decreased slightly in both resistant cell lines.


Stepwise induction of cisplatin resistance in ovarian cancer is more readily acquired in which multiple drug-resistance-associated genes are involved.

[PubMed - indexed for MEDLINE]
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