Expression Analysis for the Identification of Genes Involved in Acquired Resistance to Cisplatin in Osteosarcoma Cells

Cancer Genomics Proteomics. 2006 Nov-Dec;3(6):373-381. Epub 2006 Nov 1.

Abstract

Background: Clinical observations indicate that tumour cells can acquire tolerance when an anticancer drug is administered repeatedly. In the present study, the gene expression in cisplatin-resistant cells was analysed to identify early changes in gene expression in the course of cisplatin exposure.

Materials and methods: After establishing a cisplatin-resistant human osteosarcoma subline (OST/R) and two additional sublines by more brief repeated exposure, cDNA expression microarrays were used to study genes linked with prolonged exposure to cisplatin of human cancer cells.

Results: OST/R cells showed increased expression of 17 genes and reduced expression of 14. Genes associated with DNA repair, apoptosis, cell cycle progression, and proliferation were associated with the acquired resistance. Genes showing early changes were also identified.

Conclusion: Identification of genes showing altered expression in the early stages of development of resistance to cisplatin may help to improve the therapeutic effectiveness of this drug.

Keywords: DNA microarray; Osteosarcoma; cisplatin; drug-resistance.