The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer.
The Tetramethylpyrazine Derivative Statmp-151: A Novel Small Molecule Stat3 Inhibitor With Promising Activity Against Breast Cancer.
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DOI：
10.3389/fphar.2021.651976
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发表时间：
2021
影响因子：
5.6
通讯作者：
Gu J
中科院分区：
文献类型：
--
作者：
Fan C;Wang Y;Huang H;Li W;Ma J;Yao D;Tang Z;Xue T;Ha L;Ren Y;Zhang Y;Wang Q;Xie Y;Luo Y;Tan R;Gu J
乳腺癌是女性最常见的恶性肿瘤，是一种分子异质性疾病。信号转导子和转录激活子3（Stat 3）在包括乳腺癌在内的多种人类肿瘤中过表达和过度激活，因此代表了乳腺癌治疗的有希望的靶点。在本研究中，我们评估了一种新的Stat 3抑制剂Statmp-151在人乳腺癌细胞系MCF-7和MDA-MB-231以及小鼠乳腺癌细胞系4 T1中的活性。体外实验结果表明，Statmp-151对乳腺癌细胞株的增殖具有剂量和时间依赖性的抑制作用，对Stat 3的磷酸化具有剂量依赖性的抑制作用。流式细胞术（FCM）检测显示，Statmp-151影响线粒体膜电位和活性氧（ROS）的产生。此外，Statmp-151抑制细胞迁移，如基质金属蛋白酶MMP 2和MMP 9的分析所示。最后，在4 T1荷瘤小鼠模型中，腹膜内注射30 mg/kg/天Statmp-151显著抑制肿瘤生长，无明显毒性。这些结果表明Statmp-151可能是治疗乳腺癌的潜在候选药物。
Breast cancer is the most common malignancy in women and is a molecularly heterogeneous disease. Signal transducer and activator of transcription 3 (Stat3) is overexpressed and hyperactivated in a variety of human tumours, including breast cancer, thus representing a promising target for breast cancer treatment. In the present study, we evaluated the activities of a novel Stat3 inhibitor named Statmp-151 in the human breast cancer cell lines MCF-7 and MDA-MB-231 and the murine mammary carcinoma cell line 4T1. The in vitro results showed that Statmp-151 inhibited the proliferation of breast cancer cell lines in a dose- and time-dependent manner and suppressed the phosphorylation of Stat3 in a dose-dependent manner. Flow cytometry (FCM) assays revealed that Statmp-151 affected mitochondrial membrane potential and reactive oxygen species (ROS) production. Furthermore, Statmp-151 inhibited cell migration, as shown by analysis of the matrix metalloproteinases MMP2 and MMP9. Finally, in a 4T1 tumour-bearing mouse model, intraperitoneal injection of 30 mg/kg/day Statmp-151 significantly suppressed the growth of tumours without obvious toxicity. These results indicated that Statmp-151 might be a potential candidate for the treatment of breast cancer.
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影响因子：
6.7
作者：
Chen, Haijun;Yang, Zhengduo;Ding, Chunyong;Chu, Lili;Zhang, Yusong;Terry, Kristin;Liu, Huiling;Shen, Qiang;Zhou, Jia
通讯作者：
Zhou, Jia
影响因子：
4.2
作者：
Ji, Peng;Xu, Xin;Qiao, Chunhua
通讯作者：
Qiao, Chunhua
影响因子：
--
作者：
Zhu, Yongxia;Wei, Wei;Yu, Luoting
通讯作者：
Yu, Luoting
影响因子：
2.7
作者：
Wu, Wei;Yu, Xiao;Zheng, Dong
通讯作者：
Zheng, Dong
影响因子：
7.5
作者：
Li, Yali;Yang, Fangfang;Yin, Wenya
通讯作者：
Yin, Wenya