BML-111 inhibits EMT, migration and metastasis of TAMs-stimulated triple-negative breast cancer cells via ILK pathway.

Abstract

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. LXA4 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.

• Authors: Lan Lin, Xuliang Luo, Lin Wang, Fen Xu, Yuanqiao He, Qingyu Wang, Chunlei Yuan, Jing Xu, Liping Yan, Hua Hao
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 85 Pg. 106625 (Aug 2020) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 32485356 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier B.V. All rights reserved.

Chemical References

• 5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester
• Anti-Inflammatory Agents, Non-Steroidal
• Antigens, CD
• Antigens, Differentiation, Myelomonocytic
• CD68 antigen, human
• CDH1 protein, human
• Cadherins
• Heptanoic Acids
• Interleukin-8
• integrin-linked kinase
• GSK3B protein, human
• Glycogen Synthase Kinase 3 beta
• Protein Serine-Threonine Kinases
• Proto-Oncogene Proteins c-akt

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (pharmacology, therapeutic use)
• Antigens, CD (metabolism)
• Antigens, Differentiation, Myelomonocytic (metabolism)
• Cadherins (metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Cell Survival (drug effects)
• Epithelial-Mesenchymal Transition (drug effects)
• Female
• Glycogen Synthase Kinase 3 beta (metabolism)
• Heptanoic Acids (pharmacology, therapeutic use)
• Humans
• Interleukin-8 (metabolism)
• Lung (pathology)
• Macrophages (drug effects)
• Mice, Inbred BALB C
• Neoplasm Metastasis (prevention & control)
• Protein Serine-Threonine Kinases (metabolism)
• Proto-Oncogene Proteins c-akt (metabolism)
• Signal Transduction (drug effects)
• Triple Negative Breast Neoplasms (drug therapy, metabolism, pathology)
• Tumor Microenvironment
• Tumor-Associated Macrophages
• Xenograft Model Antitumor Assays