Zhu Hongbin, Sun Gengyun, Dong Jiahui, Fei Liming
Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical UniversityHefei 230022, Anhui, China; Chaohu Hospital of Anhui Medical UniversityChaohu 238000, Anhui, China.
Department of Respiratory Medicine, The First Affiliated Hospital of Anhui Medical University Hefei 230022, Anhui, China.
Am J Transl Res. 2017 Feb 15;9(2):396-402. eCollection 2017.
Paired related homeobox1 (PRRX1) was a newly identified Epithelial mesenchymal transition (EMT) inducer. It was found that the decreased expression of PRRX1 in breast cancer and liver cancer could enable tumor cells to obtain tumor stem cell characteristics in vitro studies. However, the role of PRRX1 in lung cancer was still unknown. The down-regulated PRRX1 gene in A549 cells was established by slow virus infection in this study. The apoptosis of A549 cells was observed after the treatment of different concentrations of cisplatin and the role of PRRX1 in the apoptosis of A549 cells was explored. MTT results showed that down-regulated PRRX1 gene could resist the inhibitory effect of cisplatin on cell proliferation. The results of flow cytometry assay showed that down-regulated PRRX1 gene could reduce the apoptosis and promote A549 cells to enter G2 phase. Mitochondrial membrane potential detection showed that PRRX1 gene could inhibit the decrease of mitochondrial membrane potential. Western blotting results showed that down-regulated PRRX1 gene could reduce the expression levels of Caspase3, caspase9, Apaf-1 and cytochrome C. In a word, down-regulation of PRRX1 could cause lung cancer cells to produce anti apoptotic ability and resistance to cisplatin, which maybe through caspase3 pathway.
配对相关同源盒1(PRRX1)是一种新发现的上皮-间质转化(EMT)诱导因子。在体外研究中发现,乳腺癌和肝癌中PRRX1表达降低可使肿瘤细胞获得肿瘤干细胞特性。然而,PRRX1在肺癌中的作用仍不清楚。本研究通过慢病毒感染建立了A549细胞中PRRX1基因下调模型。用不同浓度顺铂处理后观察A549细胞凋亡情况,并探讨PRRX1在A549细胞凋亡中的作用。MTT结果显示,PRRX1基因下调可抵抗顺铂对细胞增殖的抑制作用。流式细胞术检测结果显示,PRRX1基因下调可减少细胞凋亡并促进A549细胞进入G2期。线粒体膜电位检测显示,PRRX1基因可抑制线粒体膜电位降低。蛋白质免疫印迹结果显示,PRRX1基因下调可降低Caspase3、Caspase9、凋亡蛋白酶激活因子-1(Apaf-1)和细胞色素C的表达水平。总之,PRRX1下调可使肺癌细胞产生抗凋亡能力和顺铂耐药性,这可能是通过Caspase3途径实现的。