MACC-1 antibody target therapy suppresses growth and migration of non-small cell lung cancer

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.