ABSTRACT
Objective To explore the apoptotic effect of polyporusterone A on estrogen receptor (ER)-positive and ER-negative human breast cancer cells and the possible mechanism. Methods Three human breast cancer cell lines (MDA-MB-453, MCF-7, and BT474) were chosen in this study. MTT assay was performed to measure the relative cell viabilities. Flow cytometry was used to analyze the apoptosis and cell cycle. Western blot analysis was used to determine the expression levels of Bcl-2 family proteins. Results Cell proliferation of ER-negative human breast cancer cells was significantly inhibited by polyporusterone A in a dose-and time-dependent manner, while no significant effect was observed on the proliferation of strogen receptor (ER)-positive human breast cancer MCF-7 and BT474 cells. Moreover, polyporusterone A could reversibly arrest the MDA-MB-253 cells in G1 or G2/M phase. Flow cytometry results showed that 50 μmol/L polyporusterone A induced MDA-MB-253 cells apoptosis after treatment for 24 h, while no apoptosis occurred in MCF-7 and BT474 cell lines. Western blot results showed that 50 μmol/L polyporusterone A up-regulated the protein expression of Bad and Bax, but down-regulated the expression of Bcl-2 and Bcl-w protein. Conclusion Polyporusterone A can inhibit the proliferation of ER-negative breast cancer cells and promote apoptosis, which may be associated with the regulation of the expression of Bcl-2 family proteins.
ABSTRACT
OBJECTIVE: To investigate the different biological effects of trastuzumab and T-DM1 on BT-474 and HCC1954 cell lines. METHODS: Flow cytometry was employed to study the expression level of HER2 on the two cell lines. ELISA was used to check the binding ability of trastuzumab and T-DM1 with HER2 antigen. With cell proliferation inhibition and killing methods, the dose-response curves were explored to demonstrate the biological effects of trastuzumab and T-DM1 on the two cell lines. RESULTS: HER2 were highly expressed in both of the two cell lines. The HER2 binding ability was highly similar between trastuzumab and T-DM1. Trastuzumab could inhibit the proliferation of BT474 but not HCC1954, while T-DM1 could kill both kinds of cells. CONCLUSION: In the in vitro cell models, T-DM1 can play biological effect in HER2 highly expressed but trastuzumab-resistant cell lines.