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.
Article
de Zh
| WPRIM
| ID: wpr-242138
Bibliothèque responsable:
WPRO
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>
Texte intégral:
1
Indice:
WPRIM
Sujet Principal:
Anatomopathologie
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Transcription génétique
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Tumeurs du sein
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ARN messager
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Immunohistochimie
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Régulation négative
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Régulation de l'expression des gènes tumoraux
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Oligonucléotides antisens
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Glycoprotéine P
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Multirésistance aux médicaments
Limites du sujet:
Humans
langue:
Zh
Texte intégral:
Chinese Journal of Pathology
Année:
2003
Type:
Article