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The complexity of cancer has led to single-target agents exhibiting lower-than-desired clinical efficacy. Drugs with multiple targets provide a feasible option for the treatment of complex tumors. Multitarget anti-angiogenesis agents are among the new generation of anticancer drugs and have shown favorable clinical efficacy. Dianhydrogalactitol (DAG) is a chemotherapeutic agent for chronic myeloid leukemia and lung cancer. Recently, it has been tested in phase II trials of glioblastoma treatment; however, mechanisms of DAG in glioblastoma have not been elucidated. Here we show that DAG could inhibit the migration and invasion of U251 cell line by inhibiting matrix metalloproteinase-2 (MMP2) expression. Furthermore, DAG could also inhibit tumor angiogenesis in vitro as well as in the zebrafish model. Mechanistic studies reveal that DAG inhibited both VEGFR2 and FGFR1 pathways. Our results suggest that DAG may be a potential multitarget agent that can inhibit tumor migration, invasion, and angiogenesis, and the anti-angiogenic effects may be involved in dual-suppression VEGF/VEGFR2 and FGF2/FGFR1 signal pathways.

Background: Spinal cord injury (SCI) is a serious condition that can cause physical disability and sensory dysfunction. Cytokines play an extremely important role in the acute phase of SCI. Clarifying the cytokine expression profile is of great importance.Methods: Cytokine array analysis was used to explore the changes in 67 different proteins at 0 hours, 2 hours, 1 day, 3 days, and 7 days after acute SCI in rats. The differentially expressed cytokines in the various periods were analyzed and compared. The biological processes related to the differentially expressed proteins were examined using Gene Ontology (GO) analysis.Results: Immediately after SCI (0 hours), only ciliary neurotrophic factor (CNTF) was slightly upregulated, while 23 other proteins were down-regulated. At 2 hours after SCI, there were 3 upregulated and 21 downregulated proteins. At 1 day after SCI, there were 5 upregulated and 6 downregulated proteins.At 3 days after SCI, there were 6 upregulated and 4 downregulated proteins. At 7 days after SCI, there were 4 upregulated and 9 downregulated proteins. Erythropoietin (EPO) and Fms related tyrosine kinase 3 ligand (Flt-3L) were downregulated at all time points. CD48 was decreased at 2 hours to 7 days after SCI.Monocyte chemotactic protein-1 (MCP-1) was the only protein that was upregulated at 2 hours to 7 days.The GO and pathway analyses revealed that the cytokine-related pathways, cell death, and proliferation might play a key role during secondary SCI.Conclusions: This study identified 3 downregulated proteins during SCI, that being EPO, Flt-3L, and CD48. MCP-1 was the only upregulated protein, and its expression was upregulated till day 7 following SCI. These 4 identified genes may be potential therapeutic targets for the treatment of SCI.

Spinal cord injury is a severe central nervous system injury that results in the permanent loss of motor, sensory, and autonomic functions below the level of injury with limited recovery. The pathological process of spinal cord injury includes primary and secondary injuries, characterized by a progressive cascade. Secondary injury impairs the ability of the mitochondria to maintain homeostasis and leads to calcium overload, excitotoxicity, and oxidative stress, further exacerbating the injury. The defective mitochondrial function observed in these pathologies accelerates neuronal cell death and inhibits regeneration. Treatment of spinal cord injury by preserving mitochondrial biological function is a promising, although still underexplored, therapeutic strategy. This review aimed to explore mitochondrial-based therapeutic advances after spinal cord injury. Specifically, it briefly describes the characteristics of spinal cord injury. It then broadly discusses the drugs used to protect the mitochondria (e.g., cyclosporine A, acetyl-L-carnitine, and alpha-tocopherol), phenomena associated with mitochondrial damage processes (e.g., mitophagy, ferroptosis, and cuproptosis), mitochondrial transplantation for nerve cell regeneration, and innovative mitochondrial combined protection therapy.