Wu Dong-Ming, Liu Teng, Deng Shi-Hua, Han Rong, Zhang Ting, Li Jing, Xu Ying
Clinical Laboratory, The First Affiliated Hospital of Chengdu Medical College, Chengdu, Sichuan 610041, People's Republic of China.
Onco Targets Ther. 2020 May 4;13:3751-3763. doi: 10.2147/OTT.S242579. eCollection 2020.
Alpha-1 antitrypsin (A1AT) is a secreted protein that plays an important role in various diseases. However, the role of A1AT in non-small cell lung cancer is obscure.
A1AT expression in non-small cell lung cancer was analyzed using quantitative reverse transcription PCR, Western blotting (WB), immunohistochemistry (IHC), and ELISA. WB and IF were used to analyze markers of epithelial-to-mesenchymal transition (EMT), EndoMT, and cancer stem cell (CSC). Transwell and cell wound healing assays were used to analyze migration and invasion abilities. Colony formation and CCK-8 assays were used to analyze cell proliferation following cisplatin treatment.
A1AT expression was higher in lung cancer samples than in normal tissues and the increased expression was correlated with poor overall survival of patients. In vitro experiments showed that A1AT overexpressed by plasmid transfection significantly promoted migration, invasion, EMT, EndoMT, stemness, and colony formation in lung cancer cell lines, as opposed to A1AT downregulation by siRNA transfection, which significantly inhibited all these variables.
A1AT is a novel therapeutic target and might be associated with tumor metastasis in lung carcinoma.
α-1抗胰蛋白酶（A1AT）是一种分泌蛋白，在多种疾病中发挥重要作用。然而，A1AT在非小细胞肺癌中的作用尚不清楚。
采用定量逆转录PCR、蛋白质印迹法（WB）、免疫组织化学（IHC）和酶联免疫吸附测定（ELISA）分析非小细胞肺癌中A1AT的表达。使用WB和免疫荧光法（IF）分析上皮-间质转化（EMT）、内皮-间质转化（EndoMT）和癌症干细胞（CSC）的标志物。采用Transwell实验和细胞划痕愈合实验分析迁移和侵袭能力。采用集落形成实验和CCK-8实验分析顺铂处理后细胞的增殖情况。
肺癌样本中A1AT的表达高于正常组织，且表达增加与患者较差的总生存期相关。体外实验表明，通过质粒转染过表达A1AT可显著促进肺癌细胞系的迁移、侵袭、EMT、EndoMT、干性和集落形成，相反，通过小干扰RNA（siRNA）转染下调A1AT则可显著抑制所有这些变量。
A1AT是一种新的治疗靶点，可能与肺癌的肿瘤转移有关。
