Increased vimentin mRNA expression in MCF-7 breast cancer cell line after repeated endoxifen-treatment
Abstract: Epithelial
mesenchymal transition (EMT) plays a significant role in the development of
cancer cell resistance to drugs. Vimentin, a type III intermediate filament
protein, is a marker of EMT. Vimentin's over-expression in cancer correlates
well with increased tumor growth, change in cell shape and poor prognosis.
Endoxifen is an active metabolite of tamoxifen
and has become a new potent agent in the treatment of breast cancer. This
is a study that aimed to investigate the effect of endoxifen exposure with or
without estradiol on cell viability, cell morphology and EMT progression
through the analysis of vimentin mRNA expression after 4-week treatment.
Methods: Endoxifen, 100 nM or 1,000 nM, with or without beta-estradiol
were given repeatedly to MCF-7 cells. Cells treated with dimethyl sulfoxide
(DMSO) 0.001% were used as control. After 2- and 4-week exposure, the cells
were counted, analyzed for mRNA vimentin expression, and observed for
morphological changes.
Results: Compared to control, there were significant decreases in
vimentin mRNA expressions in endoxifen and endoxifen+β-estradiol treated cells
after 2-weeks, which then significantly increased after 4-week compared with
the 2-week exposure. We found no change in morphology of MCF-7 cells.
Conclusion: Repeated exposure of endoxifen might induce EMT progression
through increased expression of vimentin in MCF-7 breast cancer cell line.
Keywords: endoxifen; EMT;
vimentin
Author: Paramita, Melva
Louisa, Nafrialdi
Journal Code: jpkedokterangg160310