Antitumour activity of the recombination polypeptide GST-NT21MP is mediated by inhibition of CXCR4 pathway in breast cancer.
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.
Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China.
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Yang
Clinical Testing and Diagnose Experimental Center of Bengbu Medical College, Anhui 233000, China.
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Zhang
Branch of Tumour of the Center Hospital of Bengbu, Anhui 233000, China.
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Y
Ding
Clinical Testing and Diagnose Experimental Center of Bengbu Medical College, Anhui 233000, China.
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Huang
Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China.
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Chen
Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, China.
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Wu
Clinical Testing and Diagnose Experimental Center of Bengbu Medical College, Anhui 233000, China.
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Wang
1] Department of Pathology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA [2] Cyrus Tang Hematology Center, Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215123, China.
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Z
Wang
Department of Biochemistry and Molecular Biology, Bengbu Medical College, Anhui 233030, China.
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Chen
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D054426:Chemokine CXCL2 / Q000235:genetics / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008807:Mice, Inbred BALB C; D009362:Neoplasm Metastasis; D010455:Peptides / Q000235:genetics / Q000494:pharmacology*; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors* / Q000235:genetics; D011994:Recombinant Proteins / Q000494:pharmacology
D000970:Antineoplastic Agents; C527276:CXCR4 protein, human; D054426:Chemokine CXCL2; D010455:Peptides; D019718:Receptors, CXCR4; D011994:Recombinant Proteins