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MEK1/2抑制剂在作用于三阴乳腺癌(TNBC)细胞时,会负反馈引起PI3K/AKT/mTOR信号通路的激活。对于PI3K抑制剂不敏感的TNBC细胞,无法选择PI3K抑制剂和MEK1/2抑制剂联合。本研究选择联合mTOR1/2抑制剂(AZD8055)和MEK1/2抑制剂(PD0325901)作用于TNBC细胞。在MDA-MB-435细胞中,AZD8055可以抑制由PD0325901导致的PI3K通路的负反馈激活,从而完全抑制MDA-MB-435细胞中ERK1/2通路和PI3K通路的活性。DNA复制实验与细胞增殖抑制结果证明二者具有协同抑制细胞增殖的作用,细胞周期实验证明二者联合后协同引起细胞周期中的G1期阻滞。
MEK1 / 2 inhibitors negatively induce the activation of the PI3K / AKT / mTOR signaling pathway when acting on triple-negative breast cancer (TNBC) cells. For TNBC cells that are not sensitive to PI3K inhibitors, PI3K inhibitors and MEK1 / 2 inhibitors can not be selected. In this study, TNBC cells were treated with mTOR1 / 2 inhibitor (AZD8055) and MEK1 / 2 inhibitor (PD0325901). In MDA-MB-435 cells, AZD8055 inhibits the negative feedback activation of the PI3K pathway caused by PD0325901, thereby completely inhibiting the activity of ERK1 / 2 pathway and PI3K pathway in MDA-MB-435 cells. DNA replication experiments and cell proliferation inhibition results show that both have a synergistic effect on cell proliferation. Cell cycle experiments show that the combination of the two can lead to G1 phase arrest in the cell cycle.