The inhibition effects on ER− breast cancer proliferation and mechanisms illustrated in vitro were also confirmed by the in vivo study, in which initial single G-1 exposure markedly inhibited growth of ER− breast cancer cell xenograft, enhanced the expression of p53, p21, ERK1/2, and cleaved caspase-3 while decreased the expression of cyclin B and Bcl-2 in tumors. The gene discussed is MAPK3; the disease is breast cancer.