Experimental research on the development of new treatment strategies for triple negative breast cancer

三阴性乳腺癌新治疗策略开发的实验研究

• 批准号: 23591911
• 负责人: KUREBAYASHI Junichi
• 金额: $ 3.24万
• 依托单位: Kawasaki Medical School
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2011
• 资助国家: 日本
• 起止时间: 2011 至 2013
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-23591911/
• 关键词: 乳癌; トリプルネガティブ・サブタイプ; PARP阻害薬; mTOR阻害薬; 癌幹細胞; トリプルネガティブ乳癌; 抗エストロゲン薬; マイクロアレイ; 乳癌幹細胞; 内分泌療法抵抗性; トリプルネガティブ; SN38

We conducted experimental studies to investigate anti-tumor activity of a poly-ADP-ribose polymerase (PARP) 1 inhibitor olaparib and a mTOR inhibitor everolimus (EVE) using breast cancer cell lines. We also investigated the effects of the agents on the ratio of CSC. Olaparib possesses growth inhibitory activity in not only TNBC cell lines but also ER-positive, HER2-negative cell lines. A combined treatment of olaparib with antiestrogen (AE) rendered an additive growth inhibitory effect in ER-positive cell lines. Anti-tumor activity of EVE was investigated using a panel of human breast cancer cell lines of various subtypes. EVE possessed a drastic growth inhibitory effect on a BRCA1-mutated, TNBC cell line and also exhibited a moderate growth inhibitory effect on a part of ER-positive breast cancer cells lines. EVE tended to decrease the ratio of CSC in most cell lines.

我们利用乳腺癌细胞系进行了实验研究，以研究聚adp -核糖聚合酶（PARP） 1抑制剂奥拉帕尼和mTOR抑制剂依维莫司（EVE）的抗肿瘤活性。我们还研究了药剂对CSC比率的影响。奥拉帕尼不仅对TNBC细胞系具有生长抑制活性，而且对er阳性、her2阴性细胞系也具有生长抑制活性。奥拉帕尼与抗雌激素（AE）联合治疗对er阳性细胞系具有加性生长抑制作用。利用不同亚型的人乳腺癌细胞系研究了EVE的抗肿瘤活性。EVE对brca1突变的TNBC细胞系具有强烈的生长抑制作用，对部分er阳性乳腺癌细胞系也表现出适度的生长抑制作用。EVE在大多数细胞系中有降低CSC比例的趋势。