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Arch Med Res. 2011 May;42(4):281-90. doi: 10.1016/j.arcmed.2011.06.008.

MicroRNA-21 modulates chemosensitivity of breast cancer cells to doxorubicin by targeting PTEN.

Author information

1
Department of Oncology, The Second Affiliated Hospital of Nanjing Medical University, Jiangsu, PR China. wangzhaox@yahoo.com.cn

Abstract

BACKGROUND AND AIMS:

Ovexpression of microRNA-21 (miR-21) is found in various human cancers. Our aim is to investigate the association of miR-21 expression with the sensitivity of breast cancer cells to doxorubicin (ADR).

METHODS:

The half maximal inhibitory concentration (IC(50)) value of ADR in resistant MCF-7/ADR or parental MCF-7 cells was determined by MTT assay. TaqMan RT-PCR or Western blot assay was performed to detect the expression of mature miR-21 and tumor suppressor gene (PTEN) protein. MCF-7 or MCF-7/ADR cell line was transfected with miR-21mimic or inhibitor. The IC(50) value of ADR was determined. Flow cytometry and TUNEL assays were performed to analyze apoptosis. The activity of caspase-3 was analyzed.

RESULTS:

The IC(50) of ADR in MCF-7 and MCF-7/ADR cells was 0.21 ± 0.05 and 16.5 ± 0.08 μmol/L, respectively. We showed that upregulation of miR-21 in MCF-7/ADR cells was concurrent with downregulation of PTEN protein. MiR-21 mimic or inhibitor could obviously affect the sensitivity of breast cancer cells to ADR. Moreover, miR-21 inhibitor could enhance caspase-3-dependent apoptosis in MCF-7/ADR cells. Overexpression of PTEN could mimic the same effects of miR-21 inhibitor in MCF-7/ADR cells and PTEN-siRNA could increase the resistance of MCF-7 cells to ADR. MiR-21 inhibitor could increase PTEN protein expression and the luciferase activity of a PTEN 3' untranslated region-based reporter construct in MCF-7/ADR cells. PTEN-siRNA could partially reverse the increased chemosensitivity of MCF-7/ADR cells induced by miR-21 inhibitor.

CONCLUSIONS:

Dysregulation of miR-21 plays critical roles in the ADR resistance of breast cancer, at least in part via targeting PTEN.

PMID:
21820606
DOI:
10.1016/j.arcmed.2011.06.008
[Indexed for MEDLINE]

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