Phase II study of trastuzumab in combination with S-1 plus cisplatin in HER2-positive gastric cancer (HERBIS-1)
Background:CXC chemokine receptor 4 (CXCR4) and its ligand stromal cell-derived factor-1α (SDF-1α, also known as CXCL12) have important roles in promoting tumour growth and metastasis. Therefore, targeting CXCR4 could be a promising strategy for treatment of human cancer.Methods:To achieve this goal, we developed a highly purified recombination polypeptide (GST-NT21MP), which is a synthetic 21-mer peptide antagonist of CXCR4 (NT21MP) derived from the viral macrophage inflammatory protein II by fermentation technology, affinity chromatography and fast protein liquid chromatography. In this study, we used multiple methods such as MTT assay, FACS, invasion assay, RT–PCR and western blot to explore the efficacy and mechanism by which GST-NT21MP inhibits cell growth, migration and invasion of breast cancer in vitro and in vivo.Results:We found that blockade of CXCR4 pathway by GST-NT21MP decreased SDF-1-induced cell growth, adhesion and migration capacities in breast cancer cells. Moreover, GST-NT21MP significantly retarded pulmonary metastasis in vivo. Furthermore, GST-NT21MP-mediated antitumour activity was found to be associated with reduced phosphorylated Src, Akt, FAK and ERK1/2 as well as decreased Bcl-2.Conclusions:Our results suggest that GST-NT21MP could be a potential anticancer agent for the treatment of breast cancer.