Radulovic Vanja, Heider Theresa, Richter Sabine, Moertl Simone, Atkinson Michael J, Anastasov Nataša
a Institute of Radiation Biology, Helmholtz Center Munich, German Research Center for Environmental Health , Neuherberg , Germany.
b Chair of Radiation Biology , Technical University of Munich , Munich , Germany.
Int J Radiat Biol. 2017 Apr;93(4):361-372. doi: 10.1080/09553002.2016.1266057. Epub 2017 Jan 9.
MicroRNA miR-21 has emerged as a therapeutic target in the treatment of breast cancer. This study was designed to compare the responses of breast cancer cells and non-transformed breast epithelial cells to a combined regimen of miR-21 inhibition and radiation.
The MDA-MB-361 (breast cancer) and MCF-10A (non-transformed mammary epithelial) cell lines were used for the comparison in this in vitro study. The stable knockdown of miR-21 was performed by using lentiviral approach. The response of the cells was monitored 4, 24 and 48 h after the irradiation with 0.25 and 2.5 Gy, using sham-irradiated cells as controls. The response of the cells was established by performing various functional assays - cell viability and cell attachment, clonogenic survival, cell cycle analysis and 3D microtissue formation.
The knockdown of miR-21 induced significant increase in apoptosis and growth delay in MDA-MB-361 cancer cells compared to non-transformed MCF-10A cells. After combined radiation and anti-miR-21 treatment, MDA-MB-361 cells show reduced cell growth and viability what is presented in their inability to form colonies. MCF-10A cells were not as sensitive to the combined treatment and that has also been confirmed with colony forming assay.
Cellular response to a combined treatment of anti-miR-21 and radiation is different between cancer and non-cancer cells which highly support the idea of linking miR-21 inhibitor and radiation treatment in the future therapeutic approaches for breast cancer.
