Kalalinia Fatemeh, Elahian Fatemeh, Mosaffa Fatemeh, Behravan Javad
Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IRAN. ; Department of Pharmaceutical Biotechnology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IRAN.
Biotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IRAN. ; Department of Pharmaceutical Biotechnology, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, IRAN.
Iran J Pharm Res. 2014 Fall;13(4):1393-401.
Elevated expression of the drug efflux transporter ABCG2 seems to correlate with multidrug 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 multidrug 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-13-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.
药物外排转运体ABCG2的高表达似乎与癌细胞的多药耐药性相关。特异性COX-2抑制剂塞来昔布已被证明可增强癌细胞对抗癌药物的敏感性。为了阐明ABCG2抑制是否参与塞来昔布的增敏作用，我们研究了塞来昔布是否能调节乳腺癌细胞系中ABCG2的表达。分别通过实时定量逆转录-聚合酶链反应和流式细胞术分析检测多药耐药基因（ABCG2）在mRNA和蛋白质水平的表达。在三种人乳腺癌细胞系中，ABCG2和COX-2分别在MCF7-MX和MDA-MB-231细胞中高表达。COX-2抑制剂塞来昔布上调了MCF-7和MCF7-MX细胞中ABCG2 mRNA的表达，同时ABCG2蛋白表达增加。虽然塞来昔布能够阻断12-O-十四酰佛波醇-13-乙酸酯（TPA）介导的MDA-MB-231细胞中COX-2表达的增加，但它在mRNA水平将ABCG2的表达增加至对照水平的4.27倍，在蛋白质水平增加的强度较小。我们的研究结果证明塞来昔布上调人乳腺癌细胞中ABCG2的表达，并表明ABCG2不参与塞来昔布的化学增敏作用。
