Inhibitory effects of the immunoconjugate composed of anti-type IV collagenase antibody Fab' fragment and lidamycin on tumor invasion and metastasis.
- Author:
Yun FENG
1
;
Hong-Wei HE
;
Bao-Wei LI
;
Zheng-Xian ZHANG
;
Xi CHEN
;
Xiao-Fang LI
Author Information
1. School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China. fengyun76@126.com
- Publication Type:Journal Article
- MeSH:
Aminoglycosides;
pharmacology;
Animals;
Antibiotics, Antineoplastic;
pharmacology;
Antibodies, Monoclonal;
immunology;
Cell Line, Tumor;
Enediynes;
pharmacology;
Fibrosarcoma;
metabolism;
pathology;
Humans;
Immunoconjugates;
pharmacology;
Immunoglobulin Fab Fragments;
pharmacology;
Matrix Metalloproteinase 2;
immunology;
secretion;
Matrix Metalloproteinase 9;
immunology;
secretion;
Mice;
Mice, Inbred BALB C;
Mice, Nude;
Neoplasm Invasiveness;
Neoplasm Metastasis;
Neoplasm Transplantation;
RNA, Messenger;
metabolism;
Tissue Inhibitor of Metalloproteinase-1;
genetics;
metabolism;
Tumor Burden;
drug effects
- From:
Acta Pharmaceutica Sinica
2011;46(12):1462-1465
- CountryChina
- Language:Chinese
-
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.
