ABSTRACT: The development of cytostatic-drug resistance renders chemotherapy ineffective in treating ovarian cancer, the most lethal gynaecological malignancy. In many cases, it is difficult to explain the development of drug resistance based on the expression patterns of genes known to be involved in this process. Microarray-based assays can provide information about new genes that are involved in the resistance to cytostatic drugs. This report describes alterations in the level of expression of genes in cisplatin- (CisPt), doxorubicin- (Dox), topotecan- (Top), and paclitaxel- (Pac) resistant variants of W1 and A2780 ovarian cancer cell lines. These drug-resistant variants of the W1 and A2780 cell lines were generated through the stepwise selection of cells tolerant of exposure to the indicated drugs at incrementally increased concentrations. Affymetrix GeneChip Human Genome Array Strips were used for hybridization assays. The genes with significantly altered expression levels (upregulated by more than fivefold or downregulated by less than fivefold relative to the level in the parental line) in the drug-resistant sublines were selected and were filtered using volcano plotting. We observed alterations in the expression of 22 genes that were common to all three cell lines that were resistant to the same cytostatic drug. The level of expression of 13 genes was upregulated and that of nine genes was downregulated. In the CisPt-resistant cell line, we observed downregulated expression of ABCC6, BST2, ERAP2 and MCTP1; in the Pac-resistant cell line, we observe upregulated expression of ABCB1, EPHA7 and RUNDC3B and downregulated expression of LIPG, MCTP1, NSBP1, PCDH9, PTPRK and SEMA3A. The expression levels of three genes, ABCB1, ABCB4 and IFI16, were upregulated in the Dox-resistant cell lines. In the Top-resistant cell lines, we observed increased expression levels of ABCG2, HERC5, IFIH1, MYOT, S100A3, SAMD4A, SPP1 and TGFBI and decreased expression levels of MCTP1 and PTPRK
