title: 3'-Azidothymidine may potently inhibit the biosynthesis of polylactosamine chains on highly glycosylated-CD147 and reduce matrix metalloproteinase-2 expression in SGC-7901 and U251 cells.
abstract: Alterations to N‑linked glycans are closely associated with cancer progression. Of particular importance in tumor growth and invasion, is the synthesis of complex N‑linked oligosaccharides containing poly‑N‑acetyllactosamine (polylactosamine) chains, which have previously been reported to inhibit 3'‑azidothymidine (AZT). Cluster of differentiation 147 (CD147) is a glycoprotein that carries β1,6‑branched polylactosamine sugars on its N‑glycans. The present study aimed to explore the mechanism by which AZT may affect matrix metalloproteinase‑2 (MMP2) expression and the cell cycle via regulation of the N‑glycans on CD147 in SGC‑7901 and U251 cell lines. Subsequent to treatment with various concentrations of AZT, the N‑glycans of highly glycosylated (HG)‑CD147 were observed to decrease in the two cell lines, and the expression of MMP2 was also significantly decreased. In addition, cell cycle analysis demonstrated that the percentage of the cells in the G1 phase increased in a dose‑dependent manner with AZT treatment, indicating that AZT may inhibit cell proliferation in SGC‑7901 cells. It was suggested that AZT may reduce the biosynthesis of polylactosamine chains on CD147 and reduce MMP2 expression to inhibit cell proliferation in SGC‑7901 and U251 cells. Thus, AZT is suggested to be an antineoplastic drug, which may be effective therapeutically for certain types of cancer through acting on the N‑glycans of HG‑CD147.
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Xu
authors.affiliation: The Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Jianlong
authors.initials: J
authors.lastname: Ni
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Shuijun
authors.initials: S
authors.lastname: Hu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Jiang
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Chunliang
authors.initials: C
authors.lastname: Liu
authors.affiliation: The Fourth Affiliated Hospital of Soochow University, Wuxi, Jiangsu 214062, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.affiliation: Department of Biochemistry and Molecular Biology, School of Medicine, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
authors.forename: Shiliang
authors.initials: S
authors.lastname: Wu
mesh_terms: D000606:Amino Sugars / Q000096:biosynthesis*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D051926:Basigin / Q000378:metabolism; D045744:Cell Line, Tumor; D015536:Down-Regulation / Q000187:drug effects*; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006031:Glycosylation / Q000187:drug effects; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000096:biosynthesis* / Q000737:chemistry / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology*
chemical_list: D000606:Amino Sugars; D000970:Antineoplastic Agents; D011134:Polysaccharides; C066929:polylactosamine; D051926:Basigin; D015215:Zidovudine; D020778:Matrix Metalloproteinase 2