Yang B, Ma Y-F, Liu Y
Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing, China.
Drug Res (Stuttg). 2015 Oct;65(10):526-31. doi: 10.1055/s-0034-1390458. Epub 2014 Nov 4.
Over expression of ATP-binding cassette (ABC) transporter protein (ABCG2) in side population cells plays a crucial role in the chemotherapeutic drug efflux. Constitutive expression of redox sensing transcritption factor Nrf2 was shown to be involved in regulation of ABCG2 expression and chemoresistance. In the current study we made an attempt to characterize the lung adenocarcinoma SP cells.
We used FACs based Hoechst 33342 dye exclusion assay for purification of lung cancer SP cells. The sorted SP cells were subjected to drug resistance, sphere formation assays and gene expression analysis (Nrf2 and ABCG2).
We have identified 2.9% of SP cells from lung cancer whose prevalence is significantly reduced to 0.3% upon treatment with verapamil. RT-PCR and western blot analysis revealed that Nrf2 and ABCG2 were highly expressed in lung cancer SP cells. Further, these SP cells are resistant to several chemotherapeutic drugs, self-renewal, and highly tumorigenic than non-SP cells.
Our data suggest that Nrf2-mediated ABCG2 over expression in lung adenocarcinoma SP cells might responsible for chemotherapy failure. Therefore, designing novel anticancer drugs that attenuates the Nrf2 and ABCG2 expression, makes SP cells more sensitive to chemotherapy and thus prevent the tumor relapse.
三磷酸腺苷结合盒（ABC）转运蛋白（ABCG2）在侧群细胞中的过表达在化疗药物外排中起关键作用。氧化还原感应转录因子Nrf2的组成性表达被证明参与ABCG2表达的调节和化疗耐药性。在本研究中，我们试图对肺腺癌侧群细胞进行特征描述。
我们使用基于荧光激活细胞分选术（FACs）的Hoechst 33342染料排除法纯化肺癌侧群细胞。对分选得到的侧群细胞进行耐药性、成球试验和基因表达分析（Nrf2和ABCG2）。
我们从肺癌中鉴定出2.9%的侧群细胞，用维拉帕米处理后其比例显著降至0.3%。逆转录聚合酶链反应（RT-PCR）和蛋白质免疫印迹分析显示，Nrf2和ABCG2在肺癌侧群细胞中高表达。此外，这些侧群细胞对几种化疗药物具有耐药性、自我更新能力，且比非侧群细胞具有更高的致瘤性。
我们的数据表明，肺腺癌侧群细胞中Nrf2介导的ABCG2过表达可能是化疗失败的原因。因此，设计能减弱Nrf2和ABCG2表达的新型抗癌药物，可使侧群细胞对化疗更敏感，从而防止肿瘤复发。
