P53 prevent tumor invasion and metastasis by down-regulating IDO in lung cancer

Abstract

// Dongfang Tang 1 , Lu Yue 2 , Ruyong Yao 3 , Lin Zhou 4 , Yuqin Yang 4 , Liming Lu 4 and Wen Gao 1 1 Department of Thoracic Surgery, Huadong Hospital Affiliated to FuDan University, Huadong, China 2 Department of Oncology of the Qingdao Municipal Hospital, Qingdao, China 3 Central Laboratory of the Affiliated Hospital of Medical College Qingdao University, Qingdao, China 4 Central Laboratory of Shanghai Chest Hospital Affiliated to Shanghai Jiaotong University, China Correspondence to: Wen Gao, email: [e-mail] Keywords: lung cancer, IDO signaling, p53, metastasis Received: February 10, 2017      Accepted: March 29, 2017      Published: April 25, 2017 ABSTRACT 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 in vitro and metastasis assays in vivo . 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 in vivo . 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.