Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Department of Cardiothoracic Surgery, The Third People's Hospital, Yancheng, Jiangsu 224001, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7329-7336. doi: 10.3892/mmr.2017.7517. Epub 2017 Sep 19.
Non‑small‑cell lung cancer (NSCLC) accounts for ~80% of human lung cancers that result in mortalities worldwide. Metastasis‑associated in colon cancer‑1 (MACC‑1) has been demonstrated to be significantly expressed in cases of NSCLC and promotes tumor cell migration and metastasis through transactivation of the metastasis‑inducing hepatocyte growth factor/MET proto‑gene, receptor tyrosine kinase (HGF/MET) signaling pathway. The present study constructed a chimeric antibody (Chanti‑MACC‑1) targeting MACC‑1 and investigated its potential as a molecular therapeutic target in the treatment of NSCLC therapy. The expression of MACC‑1 was detected by reverse transcription‑quantitative polymerase chain reaction and western blotting in lung cancer cell lines and tissues. MTT assay was used to detect proliferation of A549 cells treated by Chanti‑MACC‑1, whereas the functional and regulatory effects of Chanti‑MACC‑1 in the migration and metastasis of NSCLC cells was investigated by a cell invasion assay. The therapeutic effect and survival time was observed in animal models. The results demonstrated that MACC‑1 expression was increased and overexpression of MACC‑1 promoted the progression of the cell cycle, significantly promoted NSCLC cell growth and enhanced tumor migration and invasion through the HGF/MET signaling pathway. It was further demonstrated that Chanti‑MACC‑1 efficiently suppressed MACC‑1 expression and significantly inhibited NSCLC cell proliferation, migration and invasion by blocking the HGF/MET signaling pathway. The data revealed that Chanti‑MACC‑1 was not only beneficial for tumor remission, however additionally contributed to the long‑term survival of NSCLC ‑bearing mice. The findings of the present study indicated that MACC‑1 was significantly upregulated and promoted tumor cell growth and migration in NSCLC cells and tissues via transactivation of the metastasis‑inducing HGF/MET signaling pathway. However, Chanti‑MACC‑1significantly inhibited tumor growth and metastasis, which suggested that MACC‑1 may be essential for tumor initiation and progression by negatively regulating tumor suppressors.
非小细胞肺癌(NSCLC)约占全球因肺癌死亡病例的 80%。研究表明,在非小细胞肺癌病例中,结肠癌转移相关基因 1(MACC-1)的表达显著上调,并通过激活促转移的肝细胞生长因子/间质上皮转化因子(HGF/MET)信号通路促进肿瘤细胞迁移和转移。本研究构建了一种针对 MACC-1 的嵌合抗体(Chanti-MACC-1),并探讨了其作为 NSCLC 治疗分子治疗靶点的潜力。通过逆转录-定量聚合酶链反应和蛋白质印迹法检测肺癌细胞系和组织中 MACC-1 的表达。采用 MTT 法检测 Chanti-MACC-1 处理 A549 细胞的增殖情况,通过细胞侵袭实验研究 Chanti-MACC-1 对 NSCLC 细胞迁移和转移的功能和调节作用。在动物模型中观察治疗效果和生存时间。结果表明,MACC-1 表达上调,MACC-1 过表达促进细胞周期进展,显著促进 NSCLC 细胞生长,并通过 HGF/MET 信号通路增强肿瘤迁移和侵袭。进一步研究表明,Chanti-MACC-1 可有效抑制 MACC-1 表达,通过阻断 HGF/MET 信号通路显著抑制 NSCLC 细胞增殖、迁移和侵袭。研究数据表明,Chanti-MACC-1 不仅有利于肿瘤缓解,而且有助于延长荷瘤小鼠的长期生存。本研究结果表明,MACC-1 在 NSCLC 细胞和组织中通过激活促转移的 HGF/MET 信号通路而上调,促进肿瘤细胞生长和迁移。然而,Chanti-MACC-1 显著抑制肿瘤生长和转移,这表明 MACC-1 可能通过负调控肿瘤抑制因子对肿瘤起始和进展至关重要。