Arsenic trioxide in the mechanism of drug resistance reversal in MCF-7/ADM cell line of human breast cancer.
- Author:
Xiuli WANG
1
;
Li KONG
;
Jinyao ZHAO
;
Peiman YANG
Author Information
- Publication Type:Journal Article
- MeSH: Antineoplastic Agents; pharmacology; Arsenicals; pharmacology; Breast Neoplasms; Dose-Response Relationship, Drug; Doxorubicin; pharmacology; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Female; Gene Expression; Glutathione S-Transferase pi; Glutathione Transferase; genetics; Humans; Isoenzymes; genetics; Oxides; pharmacology; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; Tumor Cells, Cultured
- From: Chinese Journal of Oncology 2002;24(4):339-343
- CountryChina
- Language:English
-
Abstract:
OBJECTIVETo 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.
METHODSCytotoxicity 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.
RESULTSThe 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.
CONCLUSIONAs(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.
