Galectin-1 Modulates the Survival and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) Sensitivity in Human Hepatocellular Carcinoma Cells.

Galectin-1 is a member of carbohydrate-binding proteins and plays critical roles in tumor growth and progression. It has been reported that galectin-1 is upregulated in human hepatocellular carcinoma (HCC) and facilitates HCC cell migration and invasion. In this study, the authors aimed to explore the effects of the knockdown of galectin-1 on HCC cell survival and sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). Human HCC cells were transfected with galectin-1-targeting small interfering RNA (siRNA) with or without 100 ng/mL TRAIL treatment and tested for apoptosis and gene expression changes. Cotransfection of Bcl-2- and survivin-expressing plasmids with galectin-1 siRNA was done, before TRAIL exposure, cell viability, and apoptosis were assessed. The authors found that siRNA-mediated downregulation of galectin-1 caused apoptosis in HCC cells, which was coupled with reduced Bcl-2 and survivin and increased Bax expression. Overexpression of Bcl-2 and survivin significantly blocked galectin-1 silencing-induced apoptosis of HCC cells. Knockdown of galectin-1 significantly enhanced TRAIL cytotoxicity against HCC cells, as determined by the MTT assay. Moreover, galectin-1 downregulation significantly induced apoptosis in TRAIL-treated HCC cells. Such effects were almost completely counteracted by the enforced expression of Bcl-2 and survivin. Taken together, these data first show that galectin-1 downregulation induces apoptosis in and augments TRAIL cytotoxicity to HCC cells largely through regulation of Bcl-2 and survivin expression. These findings provide a rationale for preclinical and clinical evaluation of targeting galectin-1 for improving TRAIL-based therapy against HCC.