Document Detail

Reversal of LRP-associated drug resistance in colon carcinoma SW-620 cells.
MedLine Citation:
PMID:  11149411     Owner:  NLM     Status:  MEDLINE    
Resistance to multiple drugs is mediated by lung resistance-related protein (LRP) as well as P-glycoprotein (P-gp) and multidrug resistance protein (MRP). The levels of expression of LRP mRNA and LRP in a human colon carcinoma cell line, SW-620, were increased by the differentiation-inducing agent, sodium butyrate (NaB). Treatment of SW-620 cells with NaB for 2 weeks conferred resistance to adriamycin (ADM) and VP-16. The resistance was almost completely reversed by PAK-104P, a pyridine analog, but not by cepharanthine. ADM accumulated mainly in the nuclei of SW-620 cells not treated with NaB and in the cytoplasm of SW-620 cells treated with NaB. When the NaB-treated SW-620 cells were incubated with ADM in the presence of PAK-104P, the accumulation of ADM in nuclei was substantially increased. Isolated nuclei from untreated cells accumulated more ADM than nuclei from NaB-treated cells. Efflux of ADM from the nuclei isolated from NaB-treated cells was enhanced. PAK-104P and an antibody against LRP increased the accumulation of ADM in the isolated nuclei from NaB-treated cells, and inhibited the enhanced efflux of ADM from the nuclei. These findings suggest that at least in part, PAK-104P reverses LRP-mediated drug resistance by inhibiting the efflux of ADM from nuclei. PAK-104P may be useful for reversing MDR in tumors that overexpress LRP.
M Kitazono; H Okumura; R Ikeda; T Sumizawa; T Furukawa; S Nagayama; K Seto; T Aikou; S Akiyama
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  91     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2001 Jan 
Date Detail:
Created Date:  2001-01-08     Completed Date:  2001-01-25     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  126-31     Citation Subset:  IM    
Department of Cancer Chemotherapy, Institute for Cancer Research, Kagoshima University, Japan.
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MeSH Terms
Alkaloids / pharmacology
Antineoplastic Agents / pharmacology
Antineoplastic Agents, Phytogenic / pharmacology
Butyrates / pharmacology
Carcinoma / drug therapy*
Cell Nucleus / metabolism
Colonic Neoplasms / drug therapy*
Coloring Agents / pharmacology
Cyclic P-Oxides / pharmacology*
Cytoplasm / metabolism
Dose-Response Relationship, Drug
Doxorubicin / pharmacology
Drug Resistance, Neoplasm*
Etoposide / pharmacology
Microscopy, Fluorescence
Neoplasm Proteins / metabolism*
Nicotinic Acids / pharmacology*
RNA, Catalytic / metabolism
Tetrazolium Salts / pharmacology
Thiazoles / pharmacology
Time Factors
Tumor Cells, Cultured
Vault Ribonucleoprotein Particles / metabolism*
Reg. No./Substance:
0/Alkaloids; 0/Antineoplastic Agents; 0/Antineoplastic Agents, Phytogenic; 0/Benzylisoquinolines; 0/Butyrates; 0/Coloring Agents; 0/Cyclic P-Oxides; 0/Neoplasm Proteins; 0/Nicotinic Acids; 0/RNA, Catalytic; 0/Tetrazolium Salts; 0/Thiazoles; 0/Vault Ribonucleoprotein Particles; 0/major vault protein; 116-53-0/2-methylbutyrate; 131356-86-0/PAK 104P; 23214-92-8/Doxorubicin; 298-93-1/thiazolyl blue; 33419-42-0/Etoposide; 481-49-2/cepharanthine

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