Transient silencing of galectin-3 expression promotes both in vitro and in vivo drug-induced apoptosis of human pancreatic carcinoma cells
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Tsutomu Kobayashi Tatsuo Shimura Toshiki Yajima Norio Kubo Kenichiro Araki Wataru Wada Soichi Tsutsumi Hideki Suzuki Hiroyuki Kuwano
- چاپ و سال / کشور: 2011
Description
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 b-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 GEMand 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.
Clin Exp Metastasis (2011) 28:367–376 DOI 10.1007/s10585-011-9376-x Received: 6 October 2010 / Accepted: 4 February 2011 / Published online: 18 February 2011
