Qiao En-Qi, Yang Hong-Jian
Department of Oncological Surgery, Zhejiang Cancer Hospital, Hangzhou, Zhejiang 310022, P.R. China.
Oncol Lett. 2014 Apr;7(4):1191-1196. doi: 10.3892/ol.2014.1817. Epub 2014 Jan 22.
This study was conducted to investigate the effect of increased expression of the nuclear transcription factor receptor pregnane X receptor (PXR) on drug resistance of breast cancer cells. Western blotting was used to detect the expression of PXR in breast carcinoma cells. The PXR agonist SR12813 was used to upregulate the expression of PXR. Semi-quantitative polymerase chain reaction was used to detect PXR gene expression in normal and cancerous breast tissues, as well as the expression levels of the drug-resistant genes multidrug resistance protein 1 (MDR1) and breast cancer resistance protein (BCRP) in breast cancer cells. A Cell Counting Kit-8 assay was used to observe the sensitivity of the breast cancer cells to chemotherapeutic agents. Flow cytometry was used to investigate cell apoptosis. PXR expression was detected in normal and cancerous human breast tissues and in breast cancer cell lines. SR12813 treatment led to an increased expression of PXR protein and an increased expression of drug-resistant genes, MDR1 and BCRP, in MCF-7 and MDA-MB-231 cells. SR12813 pretreatment significantly increased the resistance of MDA-MB-231 cells to docetaxel. A marked increase in resistance to 4-hydroxytamoxifen was also observed in MCF-7 with SR12813 pretreatment. Additionally, we also found that pretreatment with SR12813 led to reduced apoptosis of the two cell strains induced by chemotherapeutic agents. In conclusion, PXR expression has an important effect on the sensitivity to chemotherapy of PXR-positive breast carcinoma. The inhibitory effect of PXR on cell apoptosis may contribute to the drug resistance of breast carcinoma.
本研究旨在探讨核转录因子孕烷X受体（PXR）表达增加对乳腺癌细胞耐药性的影响。采用蛋白质免疫印迹法检测乳腺癌细胞中PXR的表达。使用PXR激动剂SR12813上调PXR的表达。采用半定量聚合酶链反应检测正常和癌性乳腺组织中PXR基因的表达，以及乳腺癌细胞中耐药基因多药耐药蛋白1（MDR1）和乳腺癌耐药蛋白（BCRP）的表达水平。使用细胞计数试剂盒-8法观察乳腺癌细胞对化疗药物的敏感性。采用流式细胞术研究细胞凋亡。检测了人正常和癌性乳腺组织以及乳腺癌细胞系中PXR的表达。SR12813处理导致MCF-7和MDA-MB-231细胞中PXR蛋白表达增加，耐药基因MDR1和BCRP的表达也增加。SR12813预处理显著增加了MDA-MB-231细胞对多西他赛的耐药性。在SR12813预处理的MCF-7细胞中，对4-羟基他莫昔芬的耐药性也显著增加。此外，我们还发现SR12813预处理导致两种细胞株经化疗药物诱导的凋亡减少。总之，PXR表达对PXR阳性乳腺癌的化疗敏感性有重要影响。PXR对细胞凋亡的抑制作用可能导致乳腺癌的耐药性。
