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目的:探讨上调核转录因子受体PXR的表达对人乳腺癌细胞MCF-7和MDA-MB-231化疗效果的影响。方法:用蛋白质印迹法检测PXR蛋白在2株乳腺癌细胞中的表达,通过PXR激动剂SR12813上调PXR受体的表达;用实时荧光定量PCR技术检测SR12813预处理前后2株细胞中耐药基因MDR1和BCRP表达的变化;CCK-8方法检测2株细胞耐药性的变化;用流式细胞术研究PXR对2株细胞凋亡的影响。结果:MCF-7和MDA-MB-231均有PXR表达;经SR12813 0.3μmol/L预处理后,2株细胞中PXR蛋白表达明显增强,耐药基因MDR1和BCRP表达显著升高(P=0.000),4-羟基他莫昔芬对MCF-7细胞48及72h的IC50分别为(11.57±0.83)和(9.70±0.68)μmol/L,多西他赛对MDA-MB-231细胞24、48和72h的IC50分别为(0.67±0.091)、(0.53±0.056)和(0.46±0.040)μg/mL,与对照组相比,均明显增加,P值均<0.05。经SR12813预处理后,药物对2株细胞诱导的凋亡率分别为(17.00±0.74)%和(7.69±0.54)%,与单药组相比,差异有统计学意义,P<0.05。结论:核转录因子受体PXR表达对PXR阳性乳腺癌的化疗敏感性具有重要影响,PXR抑制细胞凋亡可能是乳腺癌耐药的机制之一。
Objective: To investigate the effect of up-regulating the expression of nuclear factor receptor PXR on the chemotherapy effect of human breast cancer cells MCF-7 and MDA-MB-231. Methods: The expression of PXR protein in two breast cancer cells was detected by Western blotting. The expression of PXR receptor was up-regulated by PXR agonist SR12813. The drug resistance gene MDR1 in 2 cells before and after SR12813 pretreatment was detected by real-time fluorescence quantitative PCR. The change of BCRP expression was detected by CCK-8 method. The effect of PXR on the apoptosis of 2 cells was studied by flow cytometry. RESULTS: PXR expression was detected in both MCF-7 and MDA-MB-231. After pretreatment with 0.3μmol/L SR12813, the expression of PXR protein was significantly increased in both cells, and the expression of drug resistance genes MDR1 and BCRP was significantly increased (P=0.000). The IC50 of 4-hydroxytamoxifen on MCF-7 cells at 48h and 72h was (11.57±0.83) and (9.70±0.68) μmol/L, respectively. Docetaxel against MDA-MB-231 cells 24, 48 The IC50 of 72 h and 72 h were (0.67±0.091), (0.53±0.056), and (0.46±0.040) μg/mL, respectively, which were significantly increased compared with the control group. The P values were all <0.05. After SR12813 pretreatment, the apoptotic rate induced by the two drugs was (17.00±0.74)% and (7.69±0.54)%, respectively, compared with the single drug group, the difference was statistically significant (P<0.05). Conclusion: The expression of nuclear factor receptor PXR plays an important role in the chemotherapy sensitivity of PXR-positive breast cancer. PXR inhibits apoptosis may be one of the mechanisms of breast cancer resistance.