Zhang Liangyu, Fu Zelong, Li Xia, Tang Haitao, Luo Jiesi, Zhang Dehui, Zhuang Yongzhi, Han Zhiyang, Yin Mingzhu
Department of Oncology, Daqing Oil Field General Hospital, Daqing City, China.
Department of Breast surgery, Tianjin Central Obstetrics and Gynecology Hospital, Tianjin City, China.
Chem Biol Drug Des. 2017 Sep;90(3):450-455. doi: 10.1111/cbdd.12965. Epub 2017 Apr 11.
Breast cancer is one of the most invasive cancer types in female population. The functional activity of Transforming growth factor β-activated kinase 1 (TAK1) in breast cancer progression increasingly attracts attention as it provides a potential target for antibreast cancer drug development. However, the fundamental role of TAK1 for triple-negative breast cancer (TNBC) progression and the effect of potential anti-TAK1 drug candidate needs to be further evaluated. Herein, we focused on the role of TAK1 in human breast cancer cells, and we hypothesized that the inhibition of TAK1 activation can repress the growth of human TNBC cells. We found that the TAK1 is robustly activated within cancer cell population of clinic-derived TNBC samples and the human breast cancer cell lines in culture. Furthermore, we determined the effect of 5Z-7-oxozeaenol (5Z-O), a TAK1-specific small molecule inhibitor, on proliferation of human TNBC cell line. 5Z-O treatment significantly suppressed the proliferation of human TNBC cells. Collectively, these demonstrate the role of TAK1 in human breast cancer and the antiproliferate effect of TAK1 inhibitor. Our study sets the stage for further research on TAK1 as a promising target for development of anti-TNBC drugs and therapeutic strategies.
乳腺癌是女性群体中侵袭性最强的癌症类型之一。转化生长因子β激活激酶1（TAK1）在乳腺癌进展中的功能活性越来越受到关注，因为它为抗乳腺癌药物开发提供了一个潜在靶点。然而，TAK1在三阴性乳腺癌（TNBC）进展中的基本作用以及潜在的TAK1候选药物的效果仍需进一步评估。在此，我们聚焦于TAK1在人乳腺癌细胞中的作用，并假设抑制TAK1激活可抑制人TNBC细胞的生长。我们发现，TAK1在临床来源的TNBC样本的癌细胞群体以及培养的人乳腺癌细胞系中被强烈激活。此外，我们确定了TAK1特异性小分子抑制剂5Z-7-氧代玉米烯醇（5Z-O）对人TNBC细胞系增殖的影响。5Z-O处理显著抑制了人TNBC细胞的增殖。总的来说，这些结果证明了TAK1在人乳腺癌中的作用以及TAK1抑制剂的抗增殖作用。我们的研究为进一步研究TAK1作为抗TNBC药物和治疗策略开发的有前景靶点奠定了基础。
