Januchowski Radosław, Zawierucha Piotr, Ruciński Marcin, Zabel Maciej
Department of Histology and Embryology, Poznań University of Medical Sciences, Poznań 61‑781, Poland.
Oncol Rep. 2014 Nov;32(5):1981-90. doi: 10.3892/or.2014.3468. Epub 2014 Sep 9.
Ovarian cancer is the most lethal gynecological malignancy. Multiple drug resistance (MDR) development leads to resistance of cancer cells to chemotherapy. Microarray methods can provide information regarding new candidate genes that can play a role in resistance to cytostatic drugs. Extracellular matrix (ECM) can influence drug resistance by inhibiting the penetration of the drug into cancer tissue as well as increased apoptosis resistance. In the present study, we report changes in the ECM and related gene expression pattern in methotrexate-, cisplatin-, doxorubicin-, vincristine-, topotecan- and paclitaxel-resistant variants of the W1 ovarian cancer cell line. The resistant variants of the W1 cell line were generated by stepwise selection of cells with an increasing concentration of the indicated drugs. Affymetrix GeneChip® Human Genome U219 Array Strips were used for hybridizations. Independent t-tests were used to determinate the statistical significance of results. Genes whose expression levels were higher than the assumed threshold (upregulated, >5-fold and downregulated, <5-fold) were visualized using the scatter plot method, selected and listed in the tables. Among the investigated genes, expression of 24 genes increased, expression of 14 genes decreased and expression of three genes increased or decreased depending on the cell line. Among the increased genes, expression of 10 increased very significantly, >20-fold. These genes were: ITGB1BP3, COL3A1, COL5A2, COL15A1, TGFBI, DCN, LUM, MATN2, POSTN and EGFL6. The expression of seven genes decreased very significantly: ITGA1, COL1A2, LAMA2, GPC3, KRT23, VIT and HMCN1. The expression pattern of ECM and related genes provided the preliminary view into the role of ECM components in cytostatic drug resistance of cancer cells. The exact role of the investigated genes in drug resistance requires further investigation.
卵巢癌是最致命的妇科恶性肿瘤。多药耐药(MDR)的产生导致癌细胞对化疗产生抗性。微阵列方法可以提供有关可能在对细胞生长抑制剂耐药中发挥作用的新候选基因的信息。细胞外基质(ECM)可通过抑制药物渗透到癌组织以及增加抗凋亡能力来影响耐药性。在本研究中,我们报告了W1卵巢癌细胞系对甲氨蝶呤、顺铂、阿霉素、长春新碱、拓扑替康和紫杉醇耐药变体中细胞外基质及相关基因表达模式的变化。W1细胞系的耐药变体通过逐步选择用浓度递增的指定药物处理的细胞而产生。使用Affymetrix GeneChip®人类基因组U219阵列条进行杂交。采用独立t检验确定结果的统计学显著性。使用散点图法可视化表达水平高于假定阈值(上调,>5倍;下调,<5倍)的基因,进行选择并列入表格。在所研究的基因中,24个基因的表达增加,14个基因的表达减少,3个基因的表达根据细胞系不同而增加或减少。在表达增加的基因中,10个基因的表达非常显著增加,>20倍。这些基因是:ITGB1BP3、COL3A1、COL5A2、COL15A1、TGFBI、DCN、LUM、MATN2、POSTN和EGFL6。7个基因的表达非常显著降低:ITGA1、COL1A2、LAMA2、GPC3、KRT23、VIT和HMCN1。细胞外基质及相关基因的表达模式为细胞外基质成分在癌细胞对细胞生长抑制剂耐药中的作用提供了初步见解。所研究基因在耐药中的具体作用需要进一步研究。