401. MACC‑1 antibody target therapy suppresses growth and migration of non‑small cell lung cancer.
- Author
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Shi W, Song J, Wang W, Zhang Y, and Zheng S
- Subjects
- A549 Cells, Animals, Antibodies, Monoclonal genetics, Antibodies, Monoclonal metabolism, Antibodies, Monoclonal therapeutic use, Carcinoma, Non-Small-Cell Lung drug therapy, Carcinoma, Non-Small-Cell Lung metabolism, Cell Line, Tumor, Cell Movement drug effects, Down-Regulation drug effects, Epithelial-Mesenchymal Transition drug effects, Female, Hepatocyte Growth Factor metabolism, Humans, Lung Neoplasms drug therapy, Lung Neoplasms metabolism, Mice, Mice, Inbred C57BL, Microscopy, Fluorescence, Proto-Oncogene Proteins c-met metabolism, Recombinant Fusion Proteins biosynthesis, Recombinant Fusion Proteins genetics, Recombinant Fusion Proteins pharmacology, Recombinant Fusion Proteins therapeutic use, Signal Transduction drug effects, Trans-Activators, Transcription Factors genetics, Transcription Factors metabolism, Transplantation, Heterologous, Antibodies, Monoclonal pharmacology, Carcinoma, Non-Small-Cell Lung pathology, Cell Proliferation drug effects, Lung Neoplasms pathology, Transcription Factors immunology
- Abstract
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.
- Published
- 2017
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