期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 10, 期 2, 页码 463-472出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.nano.2013.08.007
关键词
Pancreatic cancer; Kras gene silencing; Arsenic therapy; Nanomedicine; Combined therapy
资金
- National Natural Science Foundation of China [81072045, 81302140, 51225305, 50830107, 20974129]
- Industry-University-Research Foundation of Guangdong Province, China [2009B090300277]
The synergetic inhibitory effects on human pancreatic cancer by nanoparticle-mediated siRNA and arsenic therapy were investigated both in vitro and in vivo. Poly(ethylene glycol)-block-poly(L-lysine) were prepared to form siRNA-complexed polyplex and poly(ethylene glycol)-block-poly(DL-lactide) were prepared to form arsenic-encapsulated vesicle, respectively. Down-regulation of the mutant Kras gene by siRNA caused defective abilities of proliferation, clonal formation, migration, and invasion of pancreatic cancer cells, as well as cell cycle arrest at the G0/G1 phase, which substantially enhanced the apoptosis-inducing effect of arsenic administration. Consequently, co-administration of the two nanomedicines encapsulating siRNA or arsenic showed ideal tumor growth inhibition both in vitro and in vivo as a result of synergistic effect of the siRNA-directed Kras oncogene silencing and arsenic-induced cell apoptosis. These results suggest that the combination of mutant Kras gene silencing and arsenic therapy using nanoparticle-mediated delivery strategy is promising for pancreatic cancer treatment. (C) 2014 Elsevier Inc. All rights reserved.
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