ABSTRACT
Elevated expression of the drug efflux transporter ABCG2 seems to correlate with multi-drug resistance of cancer cells. Specific COX-2 inhibitor celecoxib has been shown to enhance the sensitivity of cancer cells to anticancer drugs. To clarify whether ABCG2 inhibition is involved in the sensitizing effect of celecoxib, we investigated whether the expression of ABCG2 in breast cancer cell lines could be modulated by celecoxib. The expression of the multi-drug resistant gene [ABCG2] at mRNA and protein level was detected by real-time quantitative reverse transcription-polymerase chain reaction and flow cytometry analysis, respectively. Among three human breast cancer cell lines, ABCG2 and COX-2 were highly expressed in MCF7-MX and MDA-MB-231 cells, respectively. The COX-2 inhibitor celecoxib up-regulated the expression of ABCG2 mRNA in MCF-7 and MCF7-MX cells, which was accompanied by increased ABCG2 protein expression. While celecoxib was able to block the 12-O-tetradecanoylphorboL[-1]3-acetate [TPA]-mediated increase in COX-2 expression in MDA-MB-231 cells, it increased the expression of ABCG2 up to 4.27 times to the control level at mRNA level and with less intensity at protein level. Our findings provide evidence that celecoxib up-regulates ABCG2 expression in human breast cancer cells and proposed that ABCG2 is not involved in chemosensitizing effects of celecoxib
ABSTRACT
Vitiligo is a pigmentation disorder in which inflammatory mediators such as cytokines have a pivotal role in disease's pathogenesis. Interleukin 17 [IL-17A] is a proinflammatory cytokine which is involved in the induction of several proinflamatory mediators such as cyclooxygenase 2 [COX2]. The aim of this study was to investigate the gene expression of IL-17 and COX2 in peripheral blood leukocytes of vitiligo's patients. Peripheral blood leukocytes from 15 patients with vitiligo and 15 healthy controls were separated using a gradient density centrifugation method. After total RNA isolation and cDNA synthesis, IL-17 and COX2 gene expression were quantified by real-time polymerase chain reaction [PCR]. There were no significant differences in IL-17 and COX2 gene expression in lymphocytes of patients with vitiligo compared with control group [p<0.05]. However there was an increased IL-17 and COX2 gene expression in neutrophils of patients compared to controls, but it did not reach statistical significance [p=0.05]. We could not find any differences in IL-17 and Cox2 gene expression between clinical diseases subtypes, sex and age. There was a significant correlation between IL-17 and COX2 genes expression in the neutrophils of patients [p=0.00, r=0.80]. Our results showed an increased expression in IL-17 and Cox-2 genes in neurophils of patients with vitiligo. This suggested that these two factors are involved in the inflammatory process. Further studies with a larger sample size might help to establish the role of these factors in the pathogenesis of diseases