Arsenic trioxide in the mechanism of drug resistance reversal in MCF-7/ADM cell line of human breast cancer / 中华肿瘤杂志
Chinese Journal of Oncology
;
(12): 339-343, 2002.
Article
in English
| WPRIM
| ID: wpr-354028
ABSTRACT
<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Oxides
/
Pharmacology
/
Arsenicals
/
Breast Neoplasms
/
RNA, Messenger
/
Tumor Cells, Cultured
/
Doxorubicin
/
Gene Expression
/
Drug Resistance, Multiple
/
Drug Resistance, Neoplasm
Limits:
Female
/
Humans
Language:
English
Journal:
Chinese Journal of Oncology
Year:
2002
Type:
Article
Similar
MEDLINE
...
LILACS
LIS