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
Article
in English
| 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.
Full text:
Available
Index:
LILACS (Americas)
Main subject:
Doxorubicin
/
Cytokines
/
Apoptosis
/
Immunoconjugates
/
Single-Chain Antibodies
/
Antineoplastic Agents
Type of study:
Prognostic study
Limits:
Animals
/
Female
/
Humans
Language:
English
Journal:
Braz. j. med. biol. res
Journal subject:
Biology
/
Medicine
Year:
2012
Type:
Article
Affiliation country:
China
Institution/Affiliation country:
Medical School & State Key Laboratory of Pharmaceutical Biotechnology/CN
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