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.
1 Department of Infectious Disease, The First Affiliated Hospital of ZhengZhou University , ZhengZhou, China .
Juan
J
Li
1 Department of Infectious Disease, The First Affiliated Hospital of ZhengZhou University , ZhengZhou, China .
Ran-ran
RR
Sun
1 Department of Infectious Disease, The First Affiliated Hospital of ZhengZhou University , ZhengZhou, China .
Zu-jiang
ZJ
Yu
1 Department of Infectious Disease, The First Affiliated Hospital of ZhengZhou University , ZhengZhou, China .
Hongxia
H
Liang
1 Department of Infectious Disease, The First Affiliated Hospital of ZhengZhou University , ZhengZhou, China .
Shen
S
Shen
2 Department of Pharmacy, The First Affiliated Hospital of ZhengZhou University , ZhengZhou, China .
Quancheng
Q
Kan
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm; D037483:Galectin 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D055785:Gene Knockdown Techniques; D017930:Genes, Reporter; D005822:Genetic Vectors; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D008113:Liver Neoplasms / Q000473:pathology*; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000502:physiology; D034622:RNA Interference; D011994:Recombinant Proteins / Q000494:pharmacology; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D014162:Transfection
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D037483:Galectin 1; D051034:Inhibitor of Apoptosis Proteins; C445499:LGALS1 protein, human; D009363:Neoplasm Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D011994:Recombinant Proteins; D000077022:Survivin; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human
apoptosis; chemotherapy; drug resistance; galectin-1; tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)