title: [Inhibitory effects of the immunoconjugate composed of anti-type IV collagenase antibody Fab' fragment and lidamycin on tumor invasion and metastasis].
abstract: This study is to investigate the tumor invasion and metastasis inhibition effects of the immunoconjugate composed of lidamycin and anti-type IV collagenase monoclonal antibody Fab' fragment. Boyden chamber assay was used to evaluate the influence of Fab'-LDM on HT-1080 cells invasion ability, gelatinase spectrum was used to measure the change of invasion factor MMP-2 and MMP-9's secretion, and RT-PCR was adopted to determine TIMP-1 mRNA expression level. The immunoconjugate inhibition of tumor in situ metastasis was also tested in nude mice. The Fab'-LDM conjugates had dose-dependent inhibition effect on HT-1080 cells' invasion. At the concentrations of 5 and 10 nmol L(-1), the Fab'-LDM inhibited the invasion by (60 +/- 12) % and (79 +/- 11) % respectively. At the concentration of 5 and 10 nmol L(-1), the Fab'-LDM inhibited the secretion of MMP-2 by (42 +/- 8) % and (54 +/- 6) % and that of MMP-9 by (57 +/- 3) % and (87 +/- 1) %, respectively. RT-PCR indicated that conjugates increased the anti-invasion factor TIMP-1 level. The in vivo experiment showed that, compared with the control group, the tumor inhibition rate in Fab', Fab'-LDM, and LDM group equaled to (30 +/- 13) %, (86 +/- 26) %, (74 +/- 22) % respectively. In conclusion, Fab'-LDM could inhibit the invasion and metastasis of tumor and it might be a new tumor biotherapy agent.
authors.affiliation: School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China. fengyun76@126.com
authors.forename: Yun
authors.initials: Y
authors.lastname: Feng
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: He
authors.forename: Bao-Wei
authors.initials: BW
authors.lastname: Li
authors.forename: Zheng-Xian
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Xiao-Fang
authors.initials: XF
authors.lastname: Li
mesh_terms: D000617:Aminoglycosides / Q000494:pharmacology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D045744:Cell Line, Tumor; D053281:Enediynes / Q000494:pharmacology*; D005354:Fibrosarcoma / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D018796:Immunoconjugates / Q000494:pharmacology*; D007140:Immunoglobulin Fab Fragments / Q000494:pharmacology*; D020778:Matrix Metalloproteinase 2 / Q000276:immunology / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000617:Aminoglycosides; D000903:Antibiotics, Antineoplastic; D000911:Antibodies, Monoclonal; D053281:Enediynes; D018796:Immunoconjugates; D007140:Immunoglobulin Fab Fragments; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; C058024:C 1027; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9