Format

Send to

Choose Destination
See comment in PubMed Commons below
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]

Author information

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

Abstract

OBJECTIVE:

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

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.

RESULTS:

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.

CONCLUSION:

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

PMID:
11783113
[PubMed - indexed for MEDLINE]
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Loading ...
    Support Center