Transient silencing of galectin-3 expression promotes both in vitro and in vivo drug-induced apoptosis of human pancreatic carcinoma cells

Abstract

Pancreatic cancer demonstrates a strong resistance to anticancer drugs, presumably due to its resistance to drug induced apoptosis. Although gemcitabine (GEM) might be partially effective for treating advanced pancreatic cancer, its efficacy is still less than satisfactory. Galectin-3 (gal-3), a member of the β-galactoside-binding protein family, is a multifunctional protein with roles in tumor cell adhesion, proliferation, differentiation, angiogenesis, metastasis, and apoptosis. We have utilized gal-3 small interfering RNA (siRNA) to probe whether gal-3 regulates anticancer drug-induced apoptosis in pancreatic cancer cells. We found that Gal-3 siRNA augmented GEM- and cisplatin-induced apoptosis in pancreatic cancer cell lines in vitro. Mitochondrial depolarization induction was increased in gal-3-silenced cells after GEM treatment, resulting in activation of caspase-9, but not caspase-8. Akt phosphorylation was significantly downregulated in gal-3- silenced cells in association with apoptosis. Moreover, intratumoral administration of gal-3 siRNA increased the GEM sensitivity of tumor xenografts produced by subcutaneous inoculation of pancreatic cancer cells into nude mice. These results suggest that gal-3 might provide a novel therapeutic target in pancreatic cancer.

Galectin-3 gene silencing inhibits migration and invasion of human tongue cancer cells in vitro via downregulating β-catenin

“…A close correlation between Gal-3 expression and malignant metastasis/histological grade in tongue cancer has been demonstrated [12] , as well as a close correlation between Gal-3 and β-catenin in tumors [9,25] . These data suggest that β-catenin plays a key role in the invasion of several types of cancer [3][4][5][6][7][8][9][10][13][14][15][16][17] . In the SCC-4 and CAL27 cells, β-catenin was significantly inhibited at the protein level, but it was unaffected at the mRNA level.…”

“…Galectin-3 (Gal-3), a member of the carbohydrate-binding protein family, contributes to neoplastic transformation, tumor survival, angiogenesis, and metastasis [3][4][5] . Gal-3 expression is associated with tumor invasion and metastasis in various human cancers, such as gastric, colon, prostate, pancreatic, and breast cancers [6][7][8][9][10] .…”

Galectin-3 binds to CD45 on diffuse large B-cell lymphoma cells to regulate susceptibility to cell death

“…Previous studies examining the antiapoptotic activity of gal-3 have concentrated on cytoplasmic gal-3 interacting with Bcl-2 at mitochondria, while cell-surface gal-3 has been implicated in other functions, such as regulating TCR signaling and promoting T-cell death or promoting tumor cell adhesion and metastasis. 13,19,23,39,40 However, a recent study found that gal-3 acts at the cell surface to promote survival of colon adenocarcinoma cells. 41 While cytoplasmic gal-3 may also have a role in promoting survival of DLBCL cells, our findings demonstrate a clear role for cell-surface gal-3 in DLBCL cell resistance to apoptosis, and cell-surface gal-3 may be an accessible and thus more tractable therapeutic target.…”

Intranuclear accumulation of galectin-3 is associated with a poor prognosis in patients with invasive intraductal papillary mucinous neoplasm

“…The present study also highlighted the significance of gal-3-INA. Little attention has been paid to the subcellular distribution of galectin-3 in relation to patient prognosis, whereas overexpression of galectin-3 has been reported to promote various functions in tumor cells, such as anti-apoptosis, resistance to therapeutic agents, proliferation, and migration [14][15][16]30) . To establish metastatic foci, tumor cells must survive conditions such as isolation from cell-cell contact or cell-matrix adhesion.…”