Possible mechanism responsible for the acquisition of resistance to cis-diamminedichloroplatinum (II) by cultured human testicular seminoma cells.

Abstract

PURPOSE:

We established a cis-diamminedichloroplatinum (II) (CDDP) resistant cell line and determined the mechanisms of CDDP resistance.

MATERIALS AND METHODS:

The CDDP resistant cell line JKT/DDP was established from the highly metastatic human testicular seminoma cell line JKT-HM by long-term intermittent administration of low dose CDDP. Growth curves, CDDP sensitivity and intracellular CDDP concentrations were compared in JKT/DDP, the seminoma cell line JKT-1 and JKT-HM cells. Expression of the mRNA of MDR1, MRP, LRP and GST-pi was also compared.

RESULTS:

The growth curve and doubling time of JKT/DDP were similar to those of JKT-1 and JKT-HM in culture without CDDP but different with CDDP added to the culture. Morphologically cytoplasm segmentation and chromatin aggregation in JKT-1 and JKT-HM were observed when CDDP was present, while JKT/DDP cells were spindle-shaped and showed cobblestone growth. The IC50 for CDDP determined by the collagen gel drop embedded drug sensitivity test showed that JKT/DDP was more resistant to CDDP than the other 2 cell lines. The expression of MDR1, MRP and GST-pi was higher than in JKT-1 or JKT-HM cells and the intracellular CDDP concentration was lower in JKT/DDP.

CONCLUSIONS:

The JKT/DDP cell line acquired CDDP resistance by increased cytoplasmic CDDP metabolism.

• Authors: Tatsuya Kobayashi, Tomohiro Fujii, Yoshimasa Jo, Keigo Kinugawa, Masato Fujisawa
• Journal: The Journal of urology (J Urol) Vol. 171 Issue 5 Pg. 1929-33 (May 2004) ISSN: 0022-5347 [Print] United States
• PMID: 15076314 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Cisplatin

Topics

• Antineoplastic Agents (therapeutic use)
• Cisplatin (therapeutic use)
• Drug Resistance, Neoplasm
• Humans
• Male
• Seminoma (drug therapy, pathology)
• Testicular Neoplasms (drug therapy, pathology)
• Tumor Cells, Cultured