BC-ER cells showed lower Bcl-2 expression and higher Bax expression
than BC-V cells in the presence of E2 We investigated the mechanism of the resistance of BC-ER cells to chemotherapeutic agents. Western blot was performed to determine the protein expression of Bcl-2 and Bax in BC-ER and BC-V cells in the presence or absence of E2. In contrast to the effect of E2 on Bcl-2 expression in T47D cells, treatment with E2 for 12 days decreased the expression level of Bcl-2 significantly. BC-ER cells had lower Bcl-2 expression than BC-V Selleckchem CB-839 cells when treated with E2 for 12 days. Low Bax expression levels were detected in both BC-ER and BC-V cells; however, treatment with E2 induced an increase of Bax expression in BC-ER cells (Figure 5). Figure 5 Bcl-2 and Bax protein expression in BC-ER and BC-V cells.
BC-ER cells showed lower Bcl-2 expression and higher Bax expression than BC-V cells in the presence of E2 (western blot). Treatment of BC-ER cells with E2 for 12 days downregulated Bcl-2 and upregulated the Bax expression. BC-ER cells showed a lower Bcl-2/Bax ratio than BC-V PF-562271 in vitro cells in the presence of E2, which did not contribute much to greater resistance of BC-ER cells than BC-V cells. BC-ER cells grew more slowly than BC-V cells in the presence of E2 Since the Bcl-2/Bax apoptotic pathway did not contribute to the chemoresistance of BC-ER cells, we investigated the role of cell growth rate in the development of chemoresistance in BC-ER cells. In contrast to the effect of E2 on T47D cells, E2 treatment for 16 hours increased the percentage of BC-ER cells in the G1 phase and decreased the percentage of cells in the S and G2/M phases. E2 treatment for 12 days led to a marked accumulation of cells in the G1 phase. E2 treatment had no obvious influence on cell cycle distribution of BC-V cells. The percentages of BC-ER cells in the TCL S and G2/M phases were significantly lower than those of BC-V cells. E2 inhibited the proliferation of BC-ER cells as demonstrated by the growth curve. However, the growth of BC-V cells was not influenced by E2 treatment (Figure 6). In the presence of E2, BC-ER cells had lower growth potential
than BC-V cells, which may have induced the resistance of BC-ER cells to chemotherapeutic agents. Figure 6 BC-ER cells grew more slowly than BC-V cells in the presence of E2. (A, B) Cell cycle status of the BC-ER and BC-V cells. (A) Cells were treated with E2 for 16 hours before being analyzed by flow NU7026 cytometry. (B) Cells were treated with E2 for 12 days. (C) The growth curve of the BC-ER and BC-V cells was plotted for 6 days of cell culture. Discussion Several studies have reported the relationship between ERα and resistance to chemotherapeutic agents in breast cancer cells [2, 10–14]. Most papers have reported the activation of ERα by E2 upregulated expression of Bcl-2, which leads to resistance to chemotherapeutic agents in breast cancer cells.