Aims: The present study is to investigate the synergistic effect of lapatinib and luteolin in the inhibition of the growth and proliferation of breast cancer cells, as well as the underlying mechanisms.
Methods: Human breast cancer cell line BT474 was cultured in vitro. The cells were incubated with different concentrations of luteolin and/or lapatinib. MTS assay was used to test the proliferation of the cells. Flow cytometry was used to identify cell cycle. Quantitative real-time polymerase chain reaction was used to measure the expression of ERBB1 and ERBB2 mRNA. Western blotting was employed to determine the protein expression of ERBB1 and ERBB2. The phosphorylation of AKT, ERK1/2 and H2A.X, and the expression of Caspase 8 and PARP were also determined using Western blotting.
Results: Lapatinib, luteolin or the combination of both inhibited the proliferation of BT474 cells in a dose-dependent manner. Luteolin and lapatinib synergistically induced the apoptosis of BT474 cells. Combination of luteolin and lapatinib inhibited the expression of ERBB1 and ERBB2 mRNA and protein in BT474 cells. Combination of lapatinib and luteolin reduced the phosphorylation level of AKT and ERK1/2 in BT474 cells.
Conclusion: The present study demonstrates that synergistic use of luteolin with lapatinib inhibits the growth of breast cancer cells, possibly by inducing apoptosis via the deactivation of AKT and ERK signaling pathways.Author(s): Lingyan Zhang, Fan Yang, Li Huang, Aixue Liu, Jiren Zhang