4-OHT inhibits cell migration by reversal of eMT in triple negative breast cancer cells / 中国医师进修杂志

Objective To investigate whether 4-OHT could decrease the ability of invasion and metastasis by reversal of EMT in TNBC. Methods Inverted microscope was used for observing cell morphological change. Cell migration ability was measured using transwell assay. Expression of E-cadherin, Vimentin and Actin proteins were analyzed by Western blot. The distribution of E-cadherin and Vimentin were analyzed by immune- fluorescence microscopy. Relative levels of miR-200c were measured by Real-time PCR. Transient transfection was performed using Lipofectamine 2000 reagent. Animal model was established to test the migration rate of lung metastasis and metastase focals. The HE staining was performed in mice lung tissue using Immunohistochemistry to confirm the metastasis. Results 4-OHT upregulates E-cadherin expression, downregulates vimentin expression to reverse EMT in TNBC cells. 4-OHT decreases migration ability of MDA-MB-231 and MCF-7/ADR cells by transwell test to 59.4% and 43.2% ; The migration ability of cells decrease to 66.7% . 4-OHT up-regulates the expression of miR-200c in MDA-MB-231 and MCF-7/ADR cells to 280% and 450%. Inhibits expression of miR-200c, 4-OHT cannot decrease migration ability of TNBC cells. Conclusions 4-OHT could decrease the ability of invasion and metastasis, up-regulate miR-200c and reverse EMT in TNBC.

Advances in the research of pharmacogenomics of tamoxifen / 药学学报

Tamoxifen (TAM) is the most common nonsteroidal antiestrogen agent, which has been widely used in the prevention of recurrence of estrogen or progesterone receptor-positive breast cancer in patients. It is metabolized by cytochrome P450 oxidases to its active metabolite (4-hydroxytamoxifen, 4-OH-TAM) and endoxifen (EDF), which played a critical role in the therapy. 4-OH-TAM and EDF have 30-to 100-fold more potency than TAM in the suppression of estrogen-dependent breast cancer cell proliferation. CYP3A4 and CYP2D6, as the key drug-metabolizing enzymes in those metabolic actions, are known to have several alleles. Genetic polymorphisms of CYP2D6 and CYP3A4 will influence the plasma concentrations of active TAM metabolites and clinical outcomes for breast cancer patients treated with TAM. The genetic polymorphisms of drug transporters, involved in the disposition of active TAM metabolites, also have the potential to influence the plasma concentrations of active TAM metabolites and clinical outcome for the treatment of breast cancer. In this review, we summarized the association of the genetic polymorphisms in the metabolic enzymes and transporters involved in the metabolism and disposition of TAM with the metabolite concentration, efficacy and adverse effects of TAM, which provides a fundamental reference for further pharmacogenomic study and clinical use of TAM.