title: N-terminal polypeptide derived from vMIP-II exerts its antitumor activity by inhibiting the CXCR4 pathway in human glioma.
abstract: Emerging evidence demonstrates that the stromal derived factor-1 (SDF-1α)/CXCR4 axis is associated with tumor aggressiveness and metastasis, including glioma, the most common brain cancer. In the present study, we demonstrated that a novel designed peptide NT21MP of viral macrophage inflammatory protein II, targeting CXCR4 inhibits SDF-1α-induced activation in glioma. The effects of NT21MP on CXCR4 expression, cell survival and migration were assessed on the human glioma cell line U251 and SHG-44 exposed to SDF-1α, by western blotting, MTT assay, flow cytometry and transwell migration assay. Our results illustrated that NT21MP inhibited SDF-1α induced proliferation, migration and invasion by upregulated pro-apoptotic genes (Bak1 and caspase-3) and downregulated Bcl-2/Bax as well as cell cycle regulators (cyclin D1 and CDK4) to arrest cell cycle in G0/G1 phase and promote apoptosis. By RT-qPCR and immunofluorescence we found that CXCR4 was highly expressed in SHG-44 cells. Our results from wound healing and transwell invasion assays indicated silencing of CXCR4 significantly inhibited the SDF-1α‑induced migration and invasion; similarly, flow cytometry showed that treatment with si-CXCR4 affected cell cycle and induced cell apoptosis in SHG-44. However, these effects were significantly weakened by NT21MP. In conclusion, the present study indicates that NT21MP plays a regulatory role in the SDF-1α/CXCR4 axis and further manages the invasion, migration, apoptosis and cell cycle of glioma cells. Thus, NT21MP might represent a novel therapeutic approach against glioma.
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and the Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, P.R. China.
authors.forename: Qingling
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Clinical Testing and Diagnose Experimental Center of Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Haihua
authors.initials: H
authors.lastname: Wu
authors.affiliation: Clinical Testing and Diagnose Experimental Center of Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Haifeng
authors.initials: H
authors.lastname: Wang
authors.affiliation: Clinical Testing and Diagnose Experimental Center of Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Clinical Testing and Diagnose Experimental Center of Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Lingyu
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Clinical Testing and Diagnose Experimental Center of Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Zhu
authors.affiliation: Department of Biotechnology, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Wenrui
authors.initials: W
authors.lastname: Wang
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Jihong
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Bioscience, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Yingxiao
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Sulian
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Biochemistry and Molecular Biology, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China.
authors.forename: Changjie
authors.initials: C
authors.lastname: Chen
authors.affiliation: Hefei National Laboratory for Physical Sciences at Microscale and the Innovation Center for Cell Signaling Network, School of Life Sciences, University of Science and Technology of China, Hefei, Anhui 230026, P.R. China.
authors.forename: Congzhao
authors.initials: C
authors.lastname: Zhou