title: Combination of siRNA-directed Kras oncogene silencing and arsenic-induced apoptosis using a nanomedicine strategy for the effective treatment of pancreatic cancer.
abstract: 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.
  
  
  BACKGROUND
  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.
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China; Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
authors.forename: Linjuan
authors.initials: L
authors.lastname: Zeng
authors.affiliation: PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Jingguo
authors.initials: J
authors.lastname: Li
authors.affiliation: PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Chenchen
authors.initials: C
authors.lastname: Qian
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Yinting
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
authors.forename: Qiubo
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China.
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Liang
authors.affiliation: PCFM Lab of Ministry of Education, School of Chemistry and Chemical Engineering, Sun Yat-Sen University, Guangzhou 510275, China. Electronic address: shuaixt@mail.sysu.edu.cn.
authors.forename: Xintao
authors.initials: X
authors.lastname: Shuai
authors.affiliation: Department of Gastroenterology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. Electronic address: huangkaihonglaoshi@163.com.
authors.forename: Kaihong
authors.initials: K
authors.lastname: Huang
mesh_terms: D000818:Animals; D017209:Apoptosis; D001151:Arsenic / Q000737:chemistry*; D045744:Cell Line, Tumor; D002465:Cell Movement; D002470:Cell Survival; D005260:Female; D020868:Gene Silencing; D011905:Genes, ras; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D009154:Mutation; D050997:Nanomedicine; D010190:Pancreatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D011092:Polyethylene Glycols / Q000737:chemistry; D011107:Polylysine / Q000737:chemistry; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D011107:Polylysine; D011092:Polyethylene Glycols; D016283:Proto-Oncogene Proteins p21(ras); D001151:Arsenic
keywords: Arsenic therapy; Combined therapy; Kras gene silencing; Nanomedicine; Pancreatic cancer