Tang Dongfang, Yue Lu, Yao Ruyong, Zhou Lin, Yang Yuqin, Lu Liming, Gao Wen
Department of Thoracic Surgery, Huadong Hospital Affiliated to FuDan University, Huadong, China.
Department of Oncology of the Qingdao Municipal Hospital, Qingdao, China.
Oncotarget. 2017 Apr 25;8(33):54548-54557. doi: 10.18632/oncotarget.17408. eCollection 2017 Aug 15.
In present study, we are to clear demonstrate the genetic evidence of IDO signaling's impact on invasion and metastasis in lung cancer. Here we examined IDO1 expression levels in non-small cell lung cancer (NSCLC) patients (64) tumor/normal pairs underwent RT-PCR and comprehensive histological, immunohistochemica and clinical analysis. The NSCLC cells stably expressing IDO1 was analyzed for migration and invasion assays and the regulatory mechanism and metastasis assays . As results, we reported that IDO1 expression increased by more than 3.2-fold in lung cancer compared with their corresponding non-tumor tissues, and the up-regulation of IDO1 is significantly correlated to TNM stage and lymph node-metastasis. The over-expression of IDO1 significantly encouraged the metastasis and invasion of lung cancer cells, and IDO1 could promote metastasis formation . Furthermore, we further found that p53 could attenuate IDO signaling in lung cancer cell migration partly. In conclusion, these results demonstrate that the IDO signaling's impact on invasion and metastasis and the suppressive effect of p53 on IDO1 in lung cancer, present one novel therapeutic strategy for early metastatic lung cancer in clinical.
在本研究中,我们旨在明确证明吲哚胺2,3-双加氧酶(IDO)信号传导对肺癌侵袭和转移影响的遗传学证据。在此,我们检测了64例非小细胞肺癌(NSCLC)患者肿瘤/正常组织配对样本中的IDO1表达水平,并进行了全面的组织学、免疫组织化学和临床分析。对稳定表达IDO1的NSCLC细胞进行迁移和侵袭试验以及调控机制和转移试验分析。结果显示,与相应的非肿瘤组织相比,肺癌中IDO1表达增加超过3.2倍,且IDO1的上调与TNM分期和淋巴结转移显著相关。IDO1的过表达显著促进肺癌细胞的转移和侵袭,且IDO1可促进转移灶形成。此外,我们进一步发现p53可部分减弱IDO信号在肺癌细胞迁移中的作用。总之,这些结果表明IDO信号传导对侵袭和转移的影响以及p53对肺癌中IDO1的抑制作用,为临床早期转移性肺癌提供了一种新的治疗策略。