Dipalmitoylphosphatidic acid inhibits tumor growth in triple-negative breast cancer
Dipalmitoylphosphatidic acid inhibits tumor growth in triple-negative breast cancer
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二棕榈酰磷脂酸抑制三阴性乳腺癌的肿瘤生长
DOI：
10.7150/ijbs.16290
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发表时间：
2017-01-01
影响因子：
9.2
通讯作者：
Wang, Lijing
中科院分区：
文献类型：
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作者：
Zhang, Qian-Qian;Chen, Jian;Wang, Lijing
三阴性乳腺癌（TNBC）是乳腺癌的一种亚型，预后较差，约占乳腺癌病例的12-24%。越来越多的证据表明，目前还没有有效的靶向治疗TNBC。二棕榈酰磷脂酸（DPPA）是一种具有生物活性的磷脂。然而，DPPA在TNBC生长中的作用尚未被研究。在这项研究中，我们采用TNBC细胞和皮下肿瘤模型来阐明DPPA对TNBC中肿瘤生长的可能影响。我们表明，DPPA显著抑制小鼠皮下肿瘤模型中的肿瘤生长，并抑制TNBC肿瘤组织中的细胞增殖和血管生成。这种抑制部分通过抑制细胞周期蛋白B1（CCNB 1）的表达来介导，CCNB 1直接促进G2期细胞的积累并阻止人TNBC中的细胞周期进程。此外，DPPA对肿瘤生长的抑制也可能通过抑制TNBC中的肿瘤血管生成来介导。这项工作提供了初步证据，证明DPPA可能是治疗TNBC的抗肿瘤药物。
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.