Abstract:

Objective To discuss the effect of sodium selenite （SS） on the proliferation， migration， apoptosis， and tumor stemness of breast cancer doxorubicin-resistant MCF-7/ADR cells， and to clarify its mechanism. Methods After the breast cancer doxorubicin-resistant MCF-7/ADR cells were treated with various concentrations （0， 5， 10， 20， 40， and 80 μmol·L^-1） of sodium selenite （SS） for 48 h， cell counting kit-8 （CCK-8） method was used to detect the proliferation activities of the cells in various groups and the drug concentration for the subsequent experiments was determined. The MCF-7/ADR cells were divided into control group （0 μmol·L^-1 SS）， 5 μmol·L^-1 SS group， 10 μmol·L^-1 SS group， and 20 μmol·L^-1 SS group. After cultured for 24， 48， and 72 h， CCK-8 method was used to detect the proliferation activities of the cells in various groups； colony formation assay was used to detect the numbers of colony formation of the cells in various groups； flow cytometry was used to detect the apoptotic rates of the cells in various groups； wound healing assay and Transwell chamber assay were used to detect the wound healing rates and the numbers of migration cells in various groups； sphere formation assay was used to detect the numbers of sphere formation in the cells in various groups； Western blotting method was used to detect the expression levels of ATP-binding cassette transporter B subfamily member 1 （ABCB1）， microtubule-associated protein 1 light chain 3-Ⅱ （LC3-Ⅱ）， and p62 proteins in the cells in various groups. Results Compared with 0 μmol·L^-1 SS group， after cultured for 48 and 72 h， the proliferation activities of the MCF-7/ADR cells in 5， 10， 20， and 40 μmol·L^-1 SS groups were significantly decreased （P<0.01）. Compared with 0 μmol·L^-1 SS group， the numbers of clone formation cells in 10 and 20 μmol·L^-1 SS groups were significantly decreased （P<0.01）. Compared with control group， the apoptotic rates of the cells in 5， 10， and 20 μmol·L?1 SS groups showed no significant difference （P>0.05）. Compared with control group， the wound healing rates of the cells in 10 and 20 μmol·L?1 SS groups were significantly decreased （P<0.01）， and the numbers of migration cells in 5， 10， and 20 μmol·L?1 SS groups were significantly decreased （P<0.01）. After 14 d of culture， compared with control group， the numbers of spheroid formation in the cells in 5， 10， and 20 μmol·L?1 SS groups were significantly decreased （P<0.05 or P<0.01）. Compared with control group， the expression levels of ABCB1 and p62 proteins in the cells in 5， 10， and 20 μmol·L?1 SS groups were significantly decreased （P<0.05 or P<0.01）， and the expression levels of LC3-Ⅱ protein in the cells in 10 and 20 μmol·L^-1 SS groups were significantly increased （P<0.01）. Conclusion SS can inhibit the proliferation， migration， and sphere formation ability of the MCF-7/ADR cells， induce cell autophagy， and down-regulate the expression level of ABCB1 protein.

Key words: Sodium selenite, Drug resistance, Breast neoplasm, Autophagy, Doxorubicin, Cell proliferation