A conjugate of an anti-midkine single-chain variable fragment to doxorubicin inhibits tumor growth
Braz. j. med. biol. res
;
45(3): 230-237, Mar. 2012. ilus
Artigo
em Inglês
| LILACS
| ID: lil-618046
ABSTRACT
Doxorubicin (DOX) was conjugated to a single-chain variable fragment (scFv) against human midkine (MK), and the conjugate (scFv-DOX) was used to target the chemotherapeutic agent to a mouse solid tumor model in which the tumor cells expressed high levels of human MK. The His-tagged recombinant scFv was expressed in bacteria, purified by metal affinity chromatography, and then conjugated to DOX using oxidative dextran (Dex) as a linker. The molecular formula of this immunoconjugate was scFv(Dex)1.3(DOX)20. In vitro apoptosis assays showed that the scFv-DOX conjugate was more cytotoxic against MK-transfected human adenocarcinoma cells (BGC823-MK) than untransfected cells (55.3 ± 2.4 vs 22.4 ± 3.8 percent) for three independent experiments. Nude mice bearing BGC823-MK solid tumors received scFv-DOX or equivalent doses of scFv + DOX for 2 weeks and tumor growth was more effectively inhibited by the scFv-DOX conjugate than by scFv + DOX (51.83 percent inhibition vs 40.81 percent). Histological analysis of the tumor tissues revealed that the highest levels of DOX accumulated in tumors from mice treated with scFv-DOX and this resulted in more extensive tumor cell death than in animals treated with the equivalent dose of scFv + DOX. These results show that the scFv-DOX conjugate effectively inhibited tumor growth in vivo and suggest that antigen-specific scFv may be competent drug-carriers.
Texto completo:
DisponíveL
Índice:
LILACS (Américas)
Assunto principal:
Doxorrubicina
/
Citocinas
/
Apoptose
/
Imunoconjugados
/
Anticorpos de Cadeia Única
/
Antineoplásicos
Tipo de estudo:
Estudo prognóstico
Limite:
Animais
/
Feminino
/
Humanos
Idioma:
Inglês
Revista:
Braz. j. med. biol. res
Assunto da revista:
Biologia
/
Medicina
Ano de publicação:
2012
Tipo de documento:
Artigo
País de afiliação:
China
Instituição/País de afiliação:
Medical School & State Key Laboratory of Pharmaceutical Biotechnology/CN
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