Zhang Qian-Qian, Chen Jian, Zhou Da-Lei, Duan You-Fa, Qi Cui-Ling, Li Jiang-Chao, He Xiao-Dong, Zhang Min, Yang Yong-Xia, Wang Lijing
Vascular Biology Research Institute, School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
School of Basic Course, Guangdong Pharmaceutical University, Guangzhou 510006, China.
Int J Biol Sci. 2017 Mar 12;13(4):471-479. doi: 10.7150/ijbs.16290. eCollection 2017.
Triple-negative breast cancer (TNBC) is a subtype of breast cancer with a poor prognosis, accounting for approximately 12-24% of breast cancer cases. Accumulating evidence has indicated that there is no effective targeted therapy available for TNBC. Dipalmitoylphosphatidic acid (DPPA) is a bioactive phospholipid. However, the function of DPPA in the growth of TNBC has not yet been studied. In this study, we employed TNBC cells and a subcutaneous tumor model to elucidate the possible effect of DPPA on tumor growth in TNBC. We showed that DPPA significantly inhibited tumor growth in the mouse subcutaneous tumor model and suppressed cell proliferation and angiogenesis in TNBC tumor tissues. This inhibition was mediated partly by suppressing the expression of cyclin B1 (CCNB1), which directly promoted the accumulation of cells in the G2 phase and arrested cell cycle progression in human TNBC. In addition, the inhibition of tumor growth by DPPA may also be mediated by the suppression of tumor angiogenesis in TNBC. This work provides initial evidence that DPPA might be vital as an anti-tumor drug to treat TNBC.
三阴性乳腺癌(TNBC)是一种预后较差的乳腺癌亚型,约占乳腺癌病例的12%-24%。越来越多的证据表明,目前尚无针对TNBC的有效靶向治疗方法。二棕榈酰磷脂酸(DPPA)是一种生物活性磷脂。然而,DPPA在TNBC生长中的作用尚未得到研究。在本研究中,我们使用TNBC细胞和皮下肿瘤模型来阐明DPPA对TNBC肿瘤生长的可能影响。我们发现,DPPA在小鼠皮下肿瘤模型中显著抑制肿瘤生长,并抑制TNBC肿瘤组织中的细胞增殖和血管生成。这种抑制作用部分是通过抑制细胞周期蛋白B1(CCNB1)的表达介导的,CCNB1直接促进细胞在G2期的积累并阻止人TNBC细胞周期进程。此外,DPPA对肿瘤生长的抑制作用也可能是通过抑制TNBC中的肿瘤血管生成介导的。这项工作提供了初步证据,表明DPPA作为一种抗肿瘤药物治疗TNBC可能至关重要。