Overexpression of Discoidin domain receptor 1 (DDR1) is known to enhance the malignancy of breast cancer considerably. This study reports the identification of a potent DDR1 inhibitor, Nilotinib, for the treatment of breast cancer. MTT assay was used to evaluate the inhibitory activity of Nilotinib and meantime we used flow cytometry to evaluate the pro-apoptotic activity of Nilotinib against MCF-7 and MDA-MB-231. Expression of DDR1 was manipulated in MDA-MB-231 and MCF-7 cell lines with low-level DDR1 expression by transfecting with plasmids containing shRNA. The effect of DDR1 or treatment with Nilotinib on cell migration was assayed. The expression of p-DDR1, DDR1, p-ERK1/2, ERK1/2 and E-cadherin, Vimentin, Snail1, and caspase 3 were detected by western blot and immunofluorescent staining. Nilotinib against MCF-7 (IC50 = 0.403 μM) and MDA-MB-231 (IC50 = 0.819 μM) and also indicated induced apoptotic cell death. After co-culturing with Nilotinib (500 nM), apoptosis rate is 29.60 % ± 2.19% and 18.75 % ± 2.30%, respectively. Moreover, Nilotinib effectually blocked the cellular migration of MCF-7. Interestingly, the knock-down DDR1 could significantly block the migration of breast cancer, meantime the sensitivity of MCF-7 and MDA-MB-231 to Nilotinib was reduced. Targeting DDR1 therapeutically could potentially affect survival and influence metabolism in breast cancer, and Nilotinib could be used as a candidate for the treatment of breast cancer.

中文翻译：

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Nilotinib 是一种盘状结构域受体 1 (DDR1) 抑制剂，可诱导细胞凋亡并抑制乳腺癌的迁移。

已知盘状结构域受体 1 (DDR1) 的过表达会显着增强乳腺癌的恶性程度。这项研究报告了一种有效的 DDR1 抑制剂尼罗替尼的鉴定，用于治疗乳腺癌。MTT法用于评估尼罗替尼的抑制活性，同时我们使用流式细胞术评估尼罗替尼对MCF-7和MDA-MB-231的促凋亡活性。通过转染含有 shRNA 的质粒，在 DDR1 低水平表达的 MDA-MB-231 和 MCF-7 细胞系中操纵 DDR1 的表达。测定了DDR1或用尼罗替尼处理对细胞迁移的影响。通过蛋白质印迹和免疫荧光染色检测p-DDR1、DDR1、p-ERK1/2、ERK1/2和E-cadherin、Vimentin、Snail1和caspase 3的表达。尼罗替尼对抗 MCF-7 (IC50 = 0. 403 μM) 和 MDA-MB-231 (IC50 = 0.819 μM)，也表明诱导的凋亡细胞死亡。与尼罗替尼 (500 nM) 共培养后，细胞凋亡率分别为 29.60 % ± 2.19% 和 18.75 % ± 2.30%。此外，尼罗替尼有效地阻断了 MCF-7 的细胞迁移。有趣的是，敲低DDR1可以显着阻断乳腺癌的迁移，同时降低MCF-7和MDA-MB-231对尼罗替尼的敏感性。靶向 DDR1 治疗可能会影响乳腺癌的生存和代谢，尼罗替尼可用作治疗乳腺癌的候选药物。尼罗替尼有效地阻断了 MCF-7 的细胞迁移。有趣的是，敲低DDR1可以显着阻断乳腺癌的迁移，同时降低MCF-7和MDA-MB-231对尼罗替尼的敏感性。靶向 DDR1 治疗可能会影响乳腺癌的生存和代谢，尼罗替尼可用作治疗乳腺癌的候选药物。尼罗替尼有效地阻断了 MCF-7 的细胞迁移。有趣的是，敲低DDR1可以显着阻断乳腺癌的迁移，同时降低MCF-7和MDA-MB-231对尼罗替尼的敏感性。靶向 DDR1 治疗可能会影响乳腺癌的生存和代谢，尼罗替尼可用作治疗乳腺癌的候选药物。