title: Cationic liposomal co-delivery of small interfering RNA and a MEK inhibitor for enhanced anticancer efficacy.
abstract: OBJECTIVE
  To test whether co-delivery of anticancer small interfering RNA (siRNA) and a chemical MEK inhibitor using cationic liposomes enhances anticancer activity in vitro and in vivo.
  
  
  METHODS
  MEK inhibitor PD0325901 was encapsulated in lipid layers of N',N''-dioleylglutamide-based cationic liposomes (DGL). Mcl1-specific siRNA (siMcl1) was complexed to DGL or PD0325901-loaded liposomes (PDGL). Efficiency of cellular siRNA delivery was tested using fluorescent double-stranded RNA. Silencing of target proteins was evaluated using Western blotting and real-time quantitative polymerase chain reactions. In vivo anticancer activity was tested using xenografted mice.
  
  
  RESULTS
  Size and zeta potential of PDGL were similar to DGL. PDGL could deliver double-stranded RNA into cells with efficiencies comparable to DGL. Cellular co-delivery of siMcl1 and PD0325901 reduced expression of Mcl1 and pERK1/2 proteins and more effectively reduced tumor cell survival than other treatments. In mice, siMcl1 and PD0325901 co-delivered by PDGL inhibited growth of tumors 79%. Substantial apoptosis of tumor cells was observed following PDGL-mediated co-delivery of siMcl1, but not in other groups.
  
  
  CONCLUSIONS
  PDGL-mediated co-delivery of siMcl1 and MEK inhibitor, PD0325901, could serve as a potential strategy for combination chemogene anticancer therapy.
authors: School of Life Sciences and Biotechnology, Korea University, Anam-dong, Seongbuk-gu, Seoul 136-713, South Korea.
authors: Seung Hee
authors: SH
authors: Kang
authors: Hee-Jeong
authors: HJ
authors: Cho
authors: Gayong
authors: G
authors: Shim
authors: Sangbin
authors: S
authors: Lee
authors: Su-Hyeon
authors: SH
authors: Kim
authors: Han-Gon
authors: HG
authors: Choi
authors: Chan-Wha
authors: CW
authors: Kim
authors: Yu-Kyoung
authors: YK
authors: Oh
mesh_terms: D000818:Animals; D001549:Benzamides / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*; D002412:Cations / Q000378:metabolism; D045744:Cell Line, Tumor; D004159:Diphenylamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D048049:Extracellular Signal-Regulated MAP Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005260:Female; D020868:Gene Silencing; D015316:Genetic Therapy; D006801:Humans; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D002412:Cations; D008081:Liposomes; C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C506614:mirdametinib; D004159:Diphenylamine; D048049:Extracellular Signal-Regulated MAP Kinases