KU55933和KU60019对三阴性乳腺癌上皮间质转化的抑制作用及其机制的研究

Breast cancer is a malignant tumor in women. Three negative breast cancer (TNBC) was high degree of malignancy, poor prognosis, high recurrence and metastasis rate after comprehensive treatment. There is some connection between Epithelial-mesenchymal transition and metastasis, recurrence of triple negative breast cancer. There is currently no compound that is safe and highly effective in inhibiting breast cancer EMT. In our preliminary work, we found that ATM inhibitors KU55933 and KU60019 could inhibit the EMT in some TNBC cell lines and might be worked through the Akt / PI3K signaling pathway. We intend to clarify the role of KU55933 and KU60019 on the EMT and its function about cell migration, invasion, drug resistance and cancer stem cell in TNBC. Further, we will clarify the main signaling pathways and perform it in vivo on animal models. It will be a new molecular target for TNBC treatment and recurrence prevention, and it will provide a drug to inhibit metastasis and recurrence in TNBC.

乳腺癌作为一种多发于女性的恶性肿瘤，其中三阴性乳腺癌（TNBC）恶性程度高，预后差，综合治疗后的复发和转移率高。上皮间质转化与三阴性乳腺癌的转移和复发有着密切的联系。目前针对TNBC尚没有一种相对有效抑制EMT(Epithelial-mesenchymal transition)的化合物。本课题组在前期工作中发现ATM抑制剂KU55933和KU60019可以抑制部分TNBC细胞株的EMT进程，并可能通过Akt/PI3K信号通路实现其功能。我们拟在明确KU55933和KU60019对TNBC癌细胞EMT作用及其对细胞迁移、侵袭、耐药等细胞功能和肿瘤干细胞比例影响的基础上，进一步明确其作用的机制，并在动物模型上完成在体验证。以此为TNBC的治疗及复发预防明确新的分子靶点，并为TNBC治疗提供一种能够抑制肿瘤复发和转移的药物。

乳腺癌作为一种多发于女性的恶性肿瘤，其中三阴性乳腺癌（TNBC）恶性程度高，预后差，综合治疗后的复发和转移率高。上皮间质转化与三阴性乳腺癌的转移和复发有着密切的联系。目前针对TNBC尚没有一种相对有效抑制EMT(Epithelial-mesenchymal transition)的化合物。本课题组在前期工作中发现ATM抑制剂KU55933和KU60019可以抑制部分TNBC细胞株的EMT进程，并可能通过Akt/PI3K信号通路实现其功能。我们明确了KU55933和KU60019对TNBC癌细胞EMT作用及其对细胞迁移、侵袭、耐药等细胞功能和肿瘤干细胞比例影响的基础上，发现其主要通过AKT-snail信号通路起作用，并在动物模型上完成在体验证。