Document Detail

Arsenic trioxide in the mechanism of drug resistance reversal in MCF-7/ADM cell line of human breast cancer.
MedLine Citation:
PMID:  12408759     Owner:  NLM     Status:  MEDLINE    
OBJECTIVE: To investigate the effect of drug resistance by arsenic trioxide (As(2)O(3)) and its possible mechanism in human breast cancer cell line MCF-7/ADM. METHODS: Cytotoxicity of As(2)O(3) and the sensibility to adriamycin (ADM) in MCF-7/ADM cell line, a ADM-resistance cell line of human breast cancer, were studied through MTT assay. The concentration of intracellular ADM was detected by spectrofluorometry. With MCF-7/ADM cells treated with As(2)O(3) in combination with ADM, the glutathione-s-transferase (GST) activity was measured by biochemical method. The expression of GST-pi mRNA was assessed by RT-PCR. RESULTS: The non-cytotoxic dose of As(2)O(3) was 0.2 micro mol/L and the low cytotoxic dose was 0.8 micro mol/L to MCF-7/ADM cell line. 0.2 micro mol/L As(2)O(3) could significantly increase the intracellular accumulation of ADM in MCF-7/ADM cell line (P < 0.05). The medium inhibition concentration (IC(50)) was obviously reduced from 53.74 micro mol/L to 25.0 micro mol/L, with a reversal ratio of 2.1 as compared to its parental cell line. Before and after 0.2 micro mol/L, 0.8 micro mol/L As(2)O(3) were given, GST activities were decreased from 29.68 +/- 0.29 U/ml to 19.29 +/- 2.10 U/m l and 12.66 +/- 2.78 U/ml (P < 0.05). In addition, MCF-7/ADM cell line had overexpression of GST-pi mRNA. A significant down regulation of GST-pi mRNA was observed in MCF-7/ADM cells when As(2)O(3) and ADM (21.55 micro mol/L) were given for 24 hours. CONCLUSION: As(2)O(3) is able to enhance the cytotoxicity of ADM and partly reverse the ADM resistance of MCF-7/ADM cell line of human breast cancer, which may be related to the variation of GST-pi enzyme.
Xiuli Wang; Li Kong; Jinyao Zhao; Peiman Yang
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Zhonghua zhong liu za zhi [Chinese journal of oncology]     Volume:  24     ISSN:  0253-3766     ISO Abbreviation:  Zhonghua Zhong Liu Za Zhi     Publication Date:  2002 Jul 
Date Detail:
Created Date:  2002-10-31     Completed Date:  2003-01-07     Revised Date:  2005-11-17    
Medline Journal Info:
Nlm Unique ID:  7910681     Medline TA:  Zhonghua Zhong Liu Za Zhi     Country:  China    
Other Details:
Languages:  eng     Pagination:  339-43     Citation Subset:  IM    
Department of Histoembryology, Dalian Medical University, Dalian 116027, China.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Arsenicals / pharmacology*
Breast Neoplasms
Dose-Response Relationship, Drug
Doxorubicin / pharmacology*
Drug Resistance, Multiple*
Drug Resistance, Neoplasm*
Gene Expression
Glutathione S-Transferase pi
Glutathione Transferase / genetics
Isoenzymes / genetics
Oxides / pharmacology*
RNA, Messenger
Reverse Transcriptase Polymerase Chain Reaction
Tumor Cells, Cultured
Reg. No./Substance:
0/Antineoplastic Agents; 0/Arsenicals; 0/Isoenzymes; 0/Oxides; 0/RNA, Messenger; 1327-53-3/arsenic trioxide; 23214-92-8/Doxorubicin; EC protein, human; EC S-Transferase pi; EC Transferase

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