The synergistic inhibitory effect of 5-aza-2-deoxycytidine and Tamoxifen on estrogen receptor alpha negative breast cancer cell lines in vitro / 中华外科杂志
Chinese Journal of Surgery
;
(12): 1545-1549, 2005.
Article
in Chinese
| WPRIM
| ID: wpr-306071
ABSTRACT
<p><b>OBJECTIVE</b>To observe if ER alpha gene can be induced by 5-aza-CdR in ER alpha negative human breast cancer cell lines (MDA-MB-231 and MDA-MB-435) and the synergistic inhibitory effects of 5-aza-CdR and Tamoxifen on these two cell lines in vitro.</p><p><b>METHODS</b>The status of 5'CpG island methylation of ER alpha gene in ER alpha negative (MDA-MB-231 and MDA-MB-435) human breast cancer cell lines and 20 cases of breast cancer tissue was studied by MSP, the expression of ER alpha mRNA was inspected by using RT-PCR after these two cell lines were treated with 5-aza-CdR. Cell proliferation was evaluated by MTT assay, distribution of cell cycle and rate of apoptosis were determined by flow cytometry after these two cell lines were treated with 5-aza-CdR or TAM alone, or in combination in vitro.</p><p><b>RESULTS</b>The 5'CpG island is methylated in the core promotor of ER alpha gene in ER alpha negative (MDA-MB-231 and MDA-MB-435) human breast cancer cell lines and the methylating rate is 25.0%, 66.7%, 83.3%, 100% in 20 cases of breast cancer tissue of stage I, II, III, IV, respectively. The expression of ER alpha mRNA was induced in these two cell lines after treated with 5-aza-CdR, MTT array showed the proliferation activity of these two cell lines was obviously reduced in 5-aza-CdR group and the inhibitory effect on proliferation was enhanced when 5-aza-CdR combined with TAM compared with control group, the induction of apoptosis was 11.20% and 8.71% respectively by 5-aza-CdR, while the rate of apoptosis is 48.8% and 53.1% when these two cells were treated with 5-aza-CdR combined with TAM.</p><p><b>CONCLUSIONS</b>5-aza-CdR can re-express ER alpha by demethylating and sensitive ER alpha negative human breast cancer cell lines to TAM, 5-aza-CdR and TAM synergistically inhibit proliferation and induce apoptosis in ER alpha negative human breast cancer cell lines, thus offer a new way for the treatment of ER alpha negative breast cancer.</p>
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Pharmacology
/
Azacitidine
/
Tamoxifen
/
Breast Neoplasms
/
RNA, Messenger
/
Gene Expression Regulation, Neoplastic
/
Apoptosis
/
Reverse Transcriptase Polymerase Chain Reaction
/
Cell Line, Tumor
Limits:
Adult
/
Aged
/
Female
/
Humans
Language:
Chinese
Journal:
Chinese Journal of Surgery
Year:
2005
Type:
Article
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