Investigation of elemene-induced reversal of tamoxifen resistance in MCF-7 cells through oestrogen receptor α (ERα) re-expression.
Endocrine therapy is an important therapeutic approach for the treatment of oestrogen receptor (ER)-positive breast cancer. However, a number of these endocrine therapies can fail when the tumour loses its ER expression during treatment. To date, few studies have explored the potential clinical significance of traditional Chinese medicine in inducing the reversal of resistance to endocrine therapy in breast cancers. We used the ERα-negative MCF7 breast cancer cell line to create a tamoxifen (TAM)-resistant cell line, MCF7/TAM cells. After treating MCF7/TAM cells with ELE to induce the re-expression of ERα, we investigated the role and molecular mechanisms by which elemene (ELE) promotes the reversal of resistance to endocrine therapy. We discovered that treatment with 10 μg/ml ELE restored the sensitivity of MCF7/TAM cells to TAM. RT-PCR analysis revealed that ELE treatment upregulated ERα mRNA levels in MCF7/TAM cells, and immunohistochemistry confirmed the upregulation of ERα expression. Western blot analysis revealed that ELE treatment decreased the protein expression levels of Ras, MEK1/2 and p-ERK1/2 in MCF7/TAM cells. The loss of ERα expression was the primary reason for TAM resistance in MCF7 cells. The ELE-induced reversal of TAM resistance was mediated by the upregulation of ERα mRNA and the re-expression of ERα through the MAPK pathway.
Department of Oncology, The First Affiliated Hospital of Dalian Medical University, Dalian 116021, China. zhangbin_dlmu@163.com
Bin
B
Zhang
Xia
X
Zhang
Bo
B
Tang
Peishi
P
Zheng
Yang
Y
Zhang
D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects* / Q000235:genetics*; D047628:Estrogen Receptor alpha / Q000235:genetics* / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000235:genetics / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D061986:MCF-7 Cells; D012717:Sesquiterpenes / Q000494:pharmacology*; D013629:Tamoxifen / Q000494:pharmacology*
D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D012717:Sesquiterpenes; D013629:Tamoxifen; C038905:elemene