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

Autor: Yajun Zhang, Jianxiang Song, Shi-Ying Zheng, Wencai Wang, Woda Shi
Jazyk: angličtina
Rok vydání: 2017
Předmět:
0301 basic medicine
Cancer Research
chimeric antibody-metastasis-associated in colon cancer-1
Lung Neoplasms
Tumor initiation
migration
Biochemistry
Metastasis
Transactivation
Mice
0302 clinical medicine
Cell Movement
Carcinoma
Non-Small-Cell Lung
Hepatocyte Growth Factor
Antibodies
Monoclonal
Articles
Cell cycle
Proto-Oncogene Proteins c-met
Oncology
030220 oncology & carcinogenesis
Molecular Medicine
Hepatocyte growth factor
Female
medicine.drug
Signal Transduction
Epithelial-Mesenchymal Transition
Recombinant Fusion Proteins
Transplantation
Heterologous
Down-Regulation
Biology
03 medical and health sciences
Cell Line
Tumor
Genetics
medicine
metastasis
Animals
Humans
Lung cancer
Molecular Biology
metastasis-associated in colon cancer-1
Cell Proliferation
Oncogene
Cancer
medicine.disease
Molecular biology
Mice
Inbred C57BL
030104 developmental biology
non-small-cell lung cancer
Microscopy
Fluorescence
A549 Cells
Trans-Activators
Transcription Factors
Zdroj: Molecular Medicine Reports
ISSN: 1791-3004
1791-2997
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: