Department of Pathology, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China.
Department of Breast Surgery, Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi 330006, PR China.
Int Immunopharmacol. 2020 Aug;85:106625. doi: 10.1016/j.intimp.2020.106625. Epub 2020 May 30.
Triple-negative breast cancer (TNBC) has a more aggressive phenotype and higher metastasis and recurrence rates than other breast cancer subtypes. The immune microenvironment and hypoxic microenvironment of breast cancer constitute the survival environment of cancer cells, which is an important environment to support cancer cells. LXA and its analog, BML-111 is an important regulator of inflammatory cytokines, which provides a possible way for the treatment of inflammatory-related tumors. Here, in the in vitro experiment, we showed that BML-111 could inhibit the EMT and migration of TAMs-stimulated TNBC by down-regulating ILK as well as p-Akt and p-GSK3β. And it could prevent the formation of breast cancer cell clusters. In the in vivo experiment, BML-111 could inhibit the metastasis of 4T1 breast cancer cells. We also demonstrated that BML-111 could affect macrophages in tumor microenvironment to prevent metastasis. These results showed that BML-111 could be a possible candidate for breast cancer therapy by targeting ILK and TAMs.
三阴性乳腺癌（TNBC）比其他乳腺癌亚型具有更具侵袭性的表型和更高的转移和复发率。乳腺癌的免疫微环境和缺氧微环境构成了癌细胞的生存环境，这是支持癌细胞的重要环境。LXA 及其类似物 BML-111 是炎症细胞因子的重要调节剂，为治疗与炎症相关的肿瘤提供了一种可能的途径。在这里，在体外实验中，我们表明 BML-111 可以通过下调 ILK 以及 p-Akt 和 p-GSK3β 来抑制 TAMs 刺激的 TNBC 的 EMT 和迁移，并可以防止乳腺癌细胞团的形成。在体内实验中，BML-111 可以抑制 4T1 乳腺癌细胞的转移。我们还证明，BML-111 可以影响肿瘤微环境中的巨噬细胞来预防转移。这些结果表明，BML-111 可以通过靶向 ILK 和 TAMs 成为一种治疗乳腺癌的潜在候选药物。
