Overview of Galectin

Galectin family has a conservative amino acid sequence, can specifically identify β-galactoside, animal lectin family. Has been isolated, identified 15 kinds of galectin. Galectin-3 is the only chimeric type of galectin family.

Galectin-3 is widely present in normal cells and tumor cells. The interaction with various intracellular ligands and extracellular ligands involves the occurrence of tumorigenesis and the development of various mechanisms, including the adhesion, differentiation and differentiation of tumor cells. Death and transfer. Therefore, galectin-3 has become a new target for tumor diagnosis and treatment in recent years. At present, including polysaccharides, galectin-3C, peptides, antibodies, nucleic acids and other inhibitors have been developed.

Functions of Galectin-3

Galectin-3 can bind itself through the N-terminal and C-terminal interactions. The formation of dimer and multimer plays an important role in the anti-apoptotic activity of galectin-3, while galectin-3 has galectin -3 to play the anti-apoptotic effect of the Ser6 phosphorylation site.

Galectin-3C is a galectin-3 N-terminal truncated polypeptide, and soluble recombinant galectin-3C retains CRD and competes with endogenous galectin-3 for glycosyl binding sites. At the same time, galectin-3C due to the lack of N-terminal and Ser6, and can not occur self-junction and phosphorylation, thereby promoting tumor cell apoptosis, inhibition of tumor growth and metastasis. John et al. Used galectin-3C (143 amino acid residues) labeled on 35 S-labeled nude mice in human breast cancer. Galectin-3C was a competitive inhibitor of galectin-3, which significantly inhibited breast cancer Growth and metastasis, and no obvious side effects. An experimental study of the mouse SAS mixed model also confirmed the degradation of tumor growth after galectin-3C treatment. Galectin-3C treatment can reduce the primary tumor metastasis rate, but the role of metastases have been little. Has been expressed galectin-3 of the original exudative lymphoma cells, transfected galectin-3C, and further promote anti-Fas antibody-induced apoptosis, the degree of apoptosis increased by 90% to 95%.

The anti-apoptotic effect of galectin-3

A large number of studies have shown that intracellular galectin-3 can inhibit a variety of substances induced apoptosis, with the role of resistance to apoptosis. In 1996, the first reported galectin-3CDNA transfected T lymphoma cells were resistant to apoptosis induced by anti-Fas antibody or staurosporine. Subsequent studies have found that Burkitt lymphoma cells transfected with the galectin-3 expression vector are resistant to apoptosis induced by anti-Fas antibodies. Human prostate cancer cells transfected with galectin-3 expression vectors also enhanced resistance to cisplatin and etoposide-induced apoptosis. Galectin-3 also protects breast cancer cells from genistein, cisplatin, TNF-α, radiation, NO and other factors induced apoptosis and anoikis.

Galectin-3 secreted by tumor cell helps to induce tumor cell apoptosis in lymphocytes T cell apoptosis, resulting in the evolution of tumor cells escape immune regulation, thereby promoting tumor proliferation. It has been found that extracellular galectin-3 can induce human T cell apoptosis, including peripheral blood mononuclear cells. Different T cell lymphokine strains have different sensitivities to galectin-3 pro-apoptotic effects, and their own do not express galectin-3 T cell lines (such as Jurkat, CEM and MOLT-4) than high-level expression of endogenous galectin-3 Of cell lines (such as SKW6.4 and H9) are more sensitive to exogenous galectin-3.

Galectin-3 on the proliferation of T cells can promote tumor proliferation and evolution, but galectin-3 induced T cell apoptosis mechanism is quite complex. The complexes of extracellular galectin-3 and cell surface glycoprotein CD7 / CD29 can trigger mitochondria-related apoptotic signaling pathways, including the release of cytochrome c and activation of caspase-3, indicating that CD7 and CD29 play an important role in this mechanism The Galectin-3 binds to T cell death receptor CD95 (Apo-1 / Fas) protein, thereby regulating CD95-mediated apoptosis signaling pathway. Extracellular galectin-3 also binds to T cell receptors (TCR) and reduces T cell activity.

The anti-apoptosis effect of galectin-3 on different cells depends on the cell type and the nature of the stimulus. In the tumor, galectin-3 cells play an anti-tumor cell apoptosis; secretion to the extracellular galectin-3, on the one hand to induce immune cells (especially T cells) apoptosis, on the other hand Protect tumor cells from apoptosis, so as to facilitate the occurrence and development of the tumor.

Summary of Galactin-3

Glectin-3 involved in tumor cell anti-apoptotic and tumor metastasis process, is an important factor in the death of cancer patients. Thus, galectin-3 inhibitors are considered to be a novel anti-tumor drug, and inhibitors based on different strategies have shown varying degrees of antitumor effect. Sugar is currently the most promising galectin-3 inhibitor. The synthesis of galectin-3 carbohydrate inhibitors with natural ligands is simple and stable. It can be easily absorbed by the body by improving its affinity and can be used to inhibit the cell recognition by competing with endogenous galectin-3 , Angiogenesis, cell adhesion and tumor metastasis to block tumor invasion.

Most of the peptide inhibitors were designed with galectin-3 protein CRD as the target. Screened, the peptide drug screened by phage peptide library had the highest affinity for galectin-3. However, the development of galectin-3 peptide inhibitors is challenging because of the imperfect membrane stability, poor stability, short half-life in vivo, and low bioavailability. However, with the progress of protein drug efficacy research, through a reasonable route of administration to improve bioavailability, chemical modification to improve the stability of the polypeptide, or can promote the development of galectin-3 peptide inhibitors.

Galectin-3C based on the anti-tumor effect and non-toxic side effects, can be considered as a relatively safe and reliable anti-cancer drugs, but the need for further clinical research.