Academic Editor: Tiziano Maggino
Background: Current standard chemotherapy for gynecologic malignancies
consists of platinum agent and taxane though, many patients experience the
relapse of disease with drug resistance making the following therapy
unsuccessful. It’s a compelling question whether the mechanisms of doubly
resistance is a simple combination of single agent resistance or whether the core
novel mechanism common to platinum and taxane resistance stands out as a result
of combination therapy. The purpose of this study is to establish the doublet
drug resistant cell line and to find its genetic characteristics.
Methods: Platinum/taxane doublet
resistant cell lines (F3 and F4) were generated
by hybridizing two independent, platinum or taxane resistant subline (C13 or
PX24) stemmed from grand parental ME180 cells. The resistant cells were selected
through repeated exposure to cisplatin and paclitaxel. For the assessment of drug
sensitivity, colony forming assay was used. For the gene expression analysis,
genome-wide expression profiling was done using the Human Genome U133A Array.
Protein-protein interaction network (PPI) scaffold networks were retrieved from
the Search Tool for the Retrieval of Interacting Genes database and, for the
enrichment of pathway analysis, WebGestalt was used. Results: Colony
forming assay showed C13 was 5.8-fold cisplatin resistant while PX24 was 5.3-fold
paclitaxel resistant compared with parental ME180 cells. F3 and F4 acquired
resistance to cisplatin and paclitaxel by 8.3/4.9- and 3.7/3.3-fold (F3/4)
respectively. Microarray analysis demonstrated, out of 22284 genes, 103 genes
were