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人平衡型核苷载体在乳腺癌细胞中的表达情况及其对5-FU药效的影响

Effect of Human Equilibrative Nucleoside Transports on Cytotoxicity of 5-Fluorouracil in Breast Cancer Cells
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摘要 目的研究乳腺癌细胞株MDA-MB-231、MDA-MB-468、SK-BR-3、MCF-7中人平衡型核苷载体(hENTs)的表达及其对5-氟尿嘧啶(5-FU)细胞毒性的影响。方法 MDA-MB-231、MDA-MB-468、SK-BR-3、MCF-7细胞常规培养于含10%小牛血清的高糖DMEM培养液中。逆转录-聚合酶链反应(RT-PCR)检测4种细胞株中hENT1 mRNA及hENT2 mRNA的表达。每种细胞分别在含有一定浓度序列(1.28×104 ng/L^2.00×108 ng/L)5-FU的培养液中培养48 h。MTT法检测4种细胞株增殖,并计算其5-FU的半数抑制浓度(IC50)。结果①hENT1及hENT2 mRNA在MDA-MB-231、MDA-MB-468、SK-BR-3细胞中的表达均较其在MCF-7细胞中高(P<0.05),但其表达在MDA-MB-231、MDA-MB-468、SK-BR-3细胞中差异无统计学意义(P>0.05)。hENT2 mRNA表达在4种细胞中均较hENT1 mRNA表达低,差异有统计学意义(P<0.05)。②MTT结果显示,5-FU的IC50在MDAMB-231、MDA-MB-468、SK-BR-3细胞株中均较在MCF-7细胞株中低(P<0.05),在MDA-MB-231、MDA-MB-468、SK-BR-3细胞株之间差异无统计学意义(P>0.05)。③在5-FU的IC50较低的乳腺癌细胞株(MDA-MB-231、MDAMB-468、SK-BR-3)中高表达hENTs,而在5-FU的IC50较高的乳腺癌细胞株(MCF-7)中,低表达hENTs或无表达。结论在乳腺癌细胞株中,细胞膜上hENTs的表达情况能显著影响5-FU的作用效果,其结果提示,在临床上可能需要依据hENTs的表达情况来选择核苷类抗癌药物。 Objective To investigate the effect of expressions of nucleoside transporters subtype (hENT1 and hENT2) on 5-fluorouraeil (5-FU) cytotoxicity in breast cancer cell lines (MDA-MB-231, MDA-MB-468, SK-BR-3, MCF-7). Methods Four breast cancer cell lines were chosen to detect the mRNA expressions of hENT 1 and hENT2 by RT-PCR. Cells were incubated in the medium with a serial concentrations of 5-FU from 1.28 × 10^4 ng/L to 2.00 × 10^8 ng/L for 48 h. Then the cell proliferation in each cell line was measured by MTT assay and the IC50 was evaluated. Results ① The mRNA expressions of hENT1 and hENT2 in the MDA-MB-231, MDA-MB-468, or SK-BR-3 cells were signi- ficantly higher than thoes in the MCF-7 cells (P〈0. 05). The mRNA expression ofhENT2 was detected in the MDA-MB- 231, MDA-MB-468, or SK-BR-3 cells, not detected in the MCF-7 cells. ② MTT showed that IC50 of 5-FU in the MDA- MB-231, MDA-MB-468, or SK-BR-3 cells was significantly lower than that in the MCF-7 cells (P〈0. 05). There was no statistical difference of IC50 among the three lines (MDA-MB-231, MDA-MB-468, and SK-BR-3) (P〉 0. 05). ③The three lines (MDA-MB-231, MDA-MB-468, and SK-BR-3) with lower IC50 of 5-FU highly expressed hENTs, and MCF- 7 cell with the higher IC50 of 5-FU expressed less hENTs. Conclusions The expressions of hENTs in breast cancer cell lines can significantly influence 5-FU cytotoxic effect. It is implicated that the hENTs expressions might be the clue tothe choice of nucleoside anticancer drugs in clinic.
出处 《中国普外基础与临床杂志》 CAS 2014年第5期599-602,共4页 Chinese Journal of Bases and Clinics In General Surgery
关键词 细胞毒性 乳腺癌细胞株 核苷转运载体 5-氟尿嘧啶 Cytotoxicity Breast cancer cell line Nucleoside transporter 5-fluorouracil
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