Combination of siRNA-directed Kras oncogene silencing and arsenic-induced apoptosis using a nanomedicine strategy for the effective treatment of pancreatic cancer.
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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DOI：
10.1016/j.nano.2013.08.007
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发表时间：
2014-02
期刊：
影响因子：
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通讯作者：
L. Zeng;Jingguo Li;Yong Wang;Chenchen Qian;Yinting Chen;Qiu-bo Zhang;Wei Wu;Zhong Lin;Jian-zhong Liang;X. Shuai;Kaihong Huang
中科院分区：
文献类型：
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作者：
L. Zeng;Jingguo Li;Yong Wang;Chenchen Qian;Yinting Chen;Qiu-bo Zhang;Wei Wu;Zhong Lin;Jian-zhong Liang;X. Shuai;Kaihong Huang
研究纳米粒子介导的siRNA与砷治疗对人胰腺癌的体内外协同抑制作用。制备了聚乙二醇-聚赖氨酸嵌段复合物和聚乙二醇-聚丙交酯嵌段复合物，分别制备了砷囊泡。siRNA下调突变型Kras基因可导致胰腺癌细胞的增殖、克隆形成、迁移和侵袭能力下降，细胞周期阻滞于G 0/G1期，从而显著增强砷剂的促凋亡作用。因此，由于siRNA介导的Kras癌基因沉默和砷诱导的细胞凋亡的协同作用，两种封装siRNA或砷的纳米药物的共同施用在体外和体内均显示出理想的肿瘤生长抑制。这些结果表明，突变Kras基因沉默和砷治疗相结合，使用纳米粒子介导的交付策略是有希望的胰腺癌治疗。从临床编辑胰腺癌的治疗仍然是一个重大挑战。这些作者展示了一种方法，该方法将基于siRNA的Kras沉默与使用纳米颗粒向胰腺癌细胞递送砷相结合，从而增强了经处理细胞的凋亡诱导。
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 EditorTreatment 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.