Reversal of multidrug resistance property of carcinoma cells by down-regulating transcription of mdr-1 / 中华病理学杂志
Chinese Journal of Pathology
;
(12): 563-566, 2003.
Artigo
em Chinês
| WPRIM
| ID: wpr-242138
ABSTRACT
<p><b>OBJECTIVE</b>To reverse the multidrug resistance (MDR) property of carcinoma cells by blocking transcription of activating sites of mdr-1.</p><p><b>METHODS</b>Breast carcinoma cells were transinfected with several antisense oligonucleotide (ASODN) complementary to mdr-1 by lipofectin. RT-PCR was used to detect the production of mdr-1mRNA. The expression of P-glycoprotein (gp) was then detected by immunohistochemistry and the function of P-gp was detected by rhodamine123 retention.</p><p><b>RESULTS</b>Forty-eight hours after transfection, mdr-1 index of cells treated by ASODN complementary to MA zone (major initiation start zone), MI (minor initiation start zone), C zone (CAAT box), G zone (GC box) of mdr-1 gene was 1.4, 1.9, 1.6 and 2.1 respectively. The rate of P-gp protein expression in treated cells was 14%, 43%, 26% and 39% respectively. The intracellular Rh123 retention in treated cells was 125%, 83%, 102% and 77% respectively. There was significant difference between cells treated by ASODN complementary to MA zone and C zone and drug-resistant cells.</p><p><b>CONCLUSIONS</b>The ASODN complementary to MA zone and C zone of mdr-1 gene can reverse MDR of drug-resistant cells to various extent, amongst which the former is more effective. Down-regulating transcription of mdr-1 by blocking transcription activating sites can reduce the expression of mdr-1mRNA and P-gp, and thus reversing MDR of carcinoma cells. The ASODN complementary to MI zone, G zone of mdr-1 however do not significantly reverse the MDR property.</p>
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Índice:
WPRIM (Pacífico Ocidental)
Assunto principal:
Patologia
/
Transcrição Gênica
/
Neoplasias da Mama
/
RNA Mensageiro
/
Imuno-Histoquímica
/
Regulação para Baixo
/
Regulação Neoplásica da Expressão Gênica
/
Oligonucleotídeos Antissenso
/
Membro 1 da Subfamília B de Cassetes de Ligação de ATP
/
Resistência a Múltiplos Medicamentos
Limite:
Humanos
Idioma:
Chinês
Revista:
Chinese Journal of Pathology
Ano de publicação:
2003
Tipo de documento:
Artigo
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