Wang Chaokun, Deng Shuzhen, Chen Jing, Xu Xiangyun, Hu Xiaochen, Kong Dejiu, Liang Gaofeng, Yuan Xiang, Li Yuanpei, Wang Xinshuai
Henan Key Laboratory of Cancer Epigenetics, Cancer Hospital, The First Affiliated Hospital, College of Clinical Medicine, Medical College of Henan University of Science and Technology, Luoyang, China.
Medical College, Henan University of Science and Technology, Luoyang, China.
Front Oncol. 2021 May 21;11:616443. doi: 10.3389/fonc.2021.616443. eCollection 2021.
Pyrotinib (PYR) is a pan-HER kinase inhibitor that inhibits signaling the RAS/RAF/MEK/MAPK and PI3K/AKT pathways. In this study, we aimed to investigate the antitumor efficacy of pyrotinib combined with adriamycin (ADM) and explore its mechanisms on HER2 breast cancer. We investigated the effects of PYR and ADM on breast cancer and . MTT assay, Wound-healing, and transwell invasion assays were used to determine the effects of PYR, ADM or PYR combined with ADM on cell proliferation, migration, and invasion of SK-BR-3 and AU565 cells . Cell apoptosis and cycle were detected through flow cytometry. , xenograft models were established to test the effect of PYR, ADM, or the combined therapy on the nude mice. Western blotting was performed to assess the expression of Akt, p-Akt, p-65, p-p65, and FOXC1. The results indicated that PYR and ADM significantly inhibited the proliferation, migration, and invasion of SK-BR-3 and AU565 cells, and the inhibitory rate of the combination group was higher than each monotherapy group. PYR induced G1 phase cell-cycle arrest, while ADM induced G2 phase arrest, while the combination group induced G2 phase arrest. The combined treatment showed synergistic anticancer activities. Moreover, PYR significantly downregulated the expression of p-Akt, p-p65, and FOXC1. In clinical settings, PYR also exerts satisfactory efficacy against breast cancer. These findings suggest that the combination of PYR and ADM shows synergistic effects both and . PYR suppresses the proliferation, migration, and invasion of breast cancers through down-regulation of the Akt/p65/FOXC1 pathway.
吡咯替尼（PYR）是一种泛HER激酶抑制剂，可抑制RAS/RAF/MEK/MAPK和PI3K/AKT信号通路。在本研究中，我们旨在探讨吡咯替尼联合阿霉素（ADM）的抗肿瘤疗效，并探索其对HER2阳性乳腺癌的作用机制。我们研究了PYR和ADM对乳腺癌细胞的影响。采用MTT法、伤口愈合实验和Transwell侵袭实验来测定PYR、ADM或PYR联合ADM对SK-BR-3和AU565细胞增殖、迁移和侵袭的影响。通过流式细胞术检测细胞凋亡和细胞周期。此外，建立异种移植模型以测试PYR、ADM或联合治疗对裸鼠的作用。进行蛋白质免疫印迹法以评估Akt、p-Akt、p-65、p-p65和FOXC1的表达。结果表明，PYR和ADM显著抑制SK-BR-3和AU565细胞的增殖、迁移和侵袭，联合治疗组的抑制率高于各单药治疗组。PYR诱导G1期细胞周期阻滞，而ADM诱导G2期阻滞，联合治疗组诱导G2期阻滞。联合治疗显示出协同抗癌活性。此外，PYR显著下调p-Akt、p-p65和FOXC1的表达。在临床环境中，PYR对乳腺癌也具有令人满意的疗效。这些发现表明，PYR和ADM联合使用在体外和体内均显示出协同作用。PYR通过下调Akt/p65/FOXC1信号通路抑制乳腺癌细胞的增殖、迁移和侵袭。
