One-way ANOVA) (Fig. 1d). In contrast, the percentage of the G2 phase in the ES2TR160 cells treated with 160 nM paclitaxel was not U0126-EtOH supplier significantly different compared with that in the ES2TR160 cells without paclitaxel treatment (22.75 ?0.44 vs. 22.02 ?1.27 , p = 0.41, one-way ANOVA) (Fig. 1d). These results indicated that G2-M phase arrest was absent in the paclitaxel-resistant OCCC cells after being treated with a cytotoxic drug.Caspase activity in chemo-sensitive cells was higher than in chemo-resistant cells when treated with paclitaxelThe IC50 concentrations of parental ES2 cells, TOV21G, and their paclitaxel-resistant clones ES2TR160 and TOV21GTR200 cells PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/27527552 are shown in supplement Table 1. The relative resistant indices of ES2TR160 vs. ES2 and TOV21GTR200 vs. TVO21G were 9.36 and 228.3, respectively. The cell morphologies of the cell lines treated with paclitaxel are shown in Fig. 1a. Damaged morphology was noted in the ES2 cells but not in the ES2TR160 cells, including a decline in cell number, and rounded cells undergoing hydropic and vacuolated changes (Fig. 1a). Cell proliferation assays of ES2 and ES2TR160 cells treated with 160 nM of paclitaxel showed that the cell proliferative activity of the ES2 cells was significantly inhibited by paclitaxel compared with the ES2TR160 cells (Fig. 1b). The percentages of sub-G1, G1 and G2 phases among the parental ES2 and ES2TR160 cells treated with differentThe caspase activity in the tumor cells treated with paclitaxel was then evaluated. As shown in Fig. 2a, the caspase-3/7 activity in the ES2 tumor cells was significantly higher than in the ESTR160 tumor cells when treated with paclitaxel (p < 0.001, one-way ANOVA).Drug resistance-related genes in paclitaxel-resistant tumor cells were more highly expressed than in paclitaxel-sensitive tumor cellsThe expression levels of drug resistance-related genes were further evaluated by QRT RT-PCR. The expression levels of MDR1 (Fig. 2b), NANOG (Fig. 2c), HIF-1 (Fig. 2c), HIF-2 (Fig. 2c), Snai2 (Fig. 2c), TWIST1 (Fig. 2d), and ABCG2 (Fig. 2e) were significantly higher in the paclitaxelresistant cell lines ES2TR160 and TOV21GTR200 than in the paclitaxel-sensitive cell lines ES2 and TOV21G. These results indicated that genes related to drug transport,Ho et al. BMC Cancer (2015) 15:Page 5 ofFig. 1 a Morphologic changes of ES2 and ES2TR160 cells before and after paclitaxel treatment. Note: There were more floating ES2 cells than floating ES2TR160 cells. b Cell growth curves of ES2 and ES2TR160 cells treated with or without 160 nM paclitaxel by MTT assays. c The percentages of sub-G1, G1 and G2 phases among parental ES2 and ES2TR160 cells analyzed by flow cytometry. d The percentages of sub-G1, G1 and G2 phases among parental ES2 and ES2TR160 cells treated with different concentrations of paclitaxel analyzed by flow cytometrycancer stem cell characteristics, hypoxic tumor microenvironment, and epithelial-mesenchymal transition were highly expressed in the paclitaxel-resistant tumor cells.HIN-1 methylation of paclitaxel-resistant tumor cells could be reversed by a demethylating agentresistant OCCC cells was lower than that in paclitaxelsensitive OCCC cells due to the methylation of HIN-1. In addition, a demethylating agent could reverse the methylation of HIN-1 and restore its expression.Paclitaxel-resistant OCCC tissues expressed lower levels of HIN-1 than paclitaxel-sensitive OCCC tissuesChanges in the methylation status of the HIN-1 gene in paclitaxel-.