Reversão do fenótipo de resistência a múltiplas drogas em células de sarcoma uterino humano. Utilização de emulsão lipídica como veículo de oligonucleotídeos antissenso / Reversion of the multiple drug resistance phenotype in a human sarcoma cell line. Lipid emulsion as antisense oligonucleotide vector

AUTOR(ES)

Débora Levy

DATA DE PUBLICAÇÃO

2007

RESUMO

The objective of this study was to evaluate the usefulness of a nanolipid emulsion (LDE) as a vector to carry antisense oligonucleotides (OAS). LDE is a nanoemulsion consisting of 48% cholesterol esters, 47,8% phospholipid, 2,3% triglycerides and 1,9% unesterified cholesterol. It is able to obtain apoE from HDL and interact with B/E receptor. The metabolic behavior of LDE is similar to LDL. OAS are able to inhibit specific gene expression since they bind to a complementary sequence in the mRNA or in the DNA. This binding impairs the synthesis of a functional protein. The cell resistance mechanisms are present in most of normal cells, been involved in physiological process. Tumors are able to use these mechanisms to their own protection. The protein P-gp (MDR1 gene) is a glycoprotein with 170Kda that works as an organic cationic pump. We have observed that LDE was able to bind to the OAS; the binding constant was 4,2 X 10-3M-1. The complex was shown to bind to LDL receptors and then been internalized into a human sarcoma cell line resistant to doxirrubicine. After 24 hours the complex have shown citoplasmatic and nuclear distribution, after 48 hours only citoplasmatic distribution was observed. Two OAS were used. Both OAS strongly inhibited (by 70%) the cell MDR-1 gene expression after 48 hours of incubation and cells turned out to be more susceptible to doxorrubicine action. Therefore, OAS/LDE is promising complex to be used in gene therapy studies.

ASSUNTO(S)

vetores genéticos genes mdr oligonucleotídeos anti-senso emulsion emulsões resistência a múltiplas drogas antisenso oligonucleotides genetic vectors inativação gênica multiple drug resistance gene silecing genes mdr

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