[Reversal of multidrug resistance property of carcinoma cells by down-regulating transcription of mdr-1].

Abstract

OBJECTIVE:

To reverse the multidrug resistance (MDR) property of carcinoma cells by blocking transcription of activating sites of mdr-1.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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.

• Authors: Peng Gao, Geng-yin Zhou, Gang Yin, Zhi-fu Wang, Wen-jun Liu, Xiao-yan Lin
• Journal: Zhonghua bing li xue za zhi = Chinese journal of pathology (Zhonghua Bing Li Xue Za Zhi) Vol. 32 Issue 6 Pg. 563-6 (Dec 2003) ISSN: 0529-5807 [Print] China
• PMID: 14761605 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Oligonucleotides, Antisense
• RNA, Messenger

Topics

• ATP Binding Cassette Transporter, Subfamily B, Member 1 (genetics)
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Down-Regulation
• Drug Resistance, Multiple (genetics)
• Drug Resistance, Neoplasm (genetics)
• Gene Expression Regulation, Neoplastic
• Humans
• Immunohistochemistry
• Oligonucleotides, Antisense (genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Transcription, Genetic (genetics)