Combination of siRNA-directed Kras oncogene silencing and arsenic-induced apoptosis using a nanomedicine strategy for the effective treatment of pancreatic cancer
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- 作者：Linjuan Zeng ; Jingguo Li ; Yong Wang ; Chenchen Qian ; Yinting Chen ; Qiubo Zhang ; Wei Wu ; Zhong Lin ; Jianzhong Liang ; Xintao Shuai ; Kaihong Huang
- 关键词：As ; arsenic ; ATO ; arsenic trioxide ; DMEM ; Dulbecco's modified Eagle's medium ; DEPC ; diethyl pyrocarbonate ; EPR ; enhanced permeability and retention ; FBS ; fetal bovine serum ; H&E ; hematoxylin and eosin ; MTT ; 3-(4 ; 5-dimethylthiazol-2-yl)-2 ; 5-diphenyl tetrazolium bromide ; NP ; nanoparticle ; PEG-PLL ; poly(ethylene glycol)-block-poly-l-lysine ; PEG-PDLLA ; poly(ethylene glycol)-block-poly(dl-lactide) ; PBS ; phosphate-buffered saline ; RNAi ; RNA interference ; siRNA ; small interfering RNA ; SCR ; scrambled si
- 刊名：Nanomedicine: Nanotechnology, Biology and Medicine
- 出版年：February, 2014
- 年：2014
- 卷：10
- 期：2
- 页码：463-472
- 全文大小：2550 K
文摘
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.
From the Clinical Editor
Treatment of pancreatic cancer remains a major challenge. These authors demonstrate a method that combines a siRNA-based Kras silencing with arsenic delivery to pancreatic cancer cells using nanoparticles, resulting in enhanced apoptosis induction in the treated cells.