title: Dual silencing of Bcl-2 and Survivin by HSV-1 vector shows better antitumor efficacy in higher PKR phosphorylation tumor cells in vitro and in vivo.
abstract: RNA interference (RNAi) is a promising tool for cancer therapy, but its delivery strategy is a major challenge for its application. Oncolytic herpes simplex virus type 1 (HSV-1) is not only an effective antitumor drug but also an excellent vector. Herein, RNAi of oncogenes Bcl-2 and Survivin was combined with oncolytic HSV-1 (ICP34.5-/ICP6-/ICP47-/CMV-GM-CSF) and a new vector HSV010-BS was constructed. Transfected cell viability assays and animal experiments revealed that the dual silencing of Bcl-2 and Survivin improved the antitumor effect of oncolytic HSV-1 in vitro and in vivo, while the antitumor effect was correlated with the phosphorylation levels of PKR of the tumor cells. The higher the phosphorylation levels of PKR of the tumor cells, the weaker the replication ability of oncolytic HSV-1, and the more powerful HSV010-BS was than its control vectors in inhibiting the growth of the tumor cells. The results provided direct supportive proofs for a new potential cancer therapy strategy.
authors.affiliation: 1] OrienGene Biotechnology Ltd, Beijing, P.R.China [2] Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing, P.R.China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: 1] SinoGenoMax Co., Ltd./Chinese National Human Genome Center, Beijing, P.R.China [2] Beijing Key Lab of Genomics, Beijing, P.R.China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: OrienGene Biotechnology Ltd, Beijing, P.R.China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing, P.R.China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing, P.R.China.
authors.forename: J
authors.initials: J
authors.lastname: Yang
authors.affiliation: Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing, P.R.China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhai
authors.affiliation: 1] Key Laboratory for Cell Proliferation and Regulation Biology of State Education Ministry, College of Life Sciences, Beijing Normal University, Beijing, P.R.China [2] SinoGenoMax Co., Ltd./Chinese National Human Genome Center, Beijing, P.R.China [3] Beijing Key Lab of Genomics, Beijing, P.R.China.
authors.forename: B
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor / Q000187:drug effects; D005260:Female; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors / Q000494:pharmacology*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics* / Q000378:metabolism; D008819:Mice, Nude; D058990:Molecular Targeted Therapy / Q000379:methods*; D050130:Oncolytic Virotherapy / Q000379:methods*; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D000077022:Survivin; D019892:eIF-2 Kinase / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; D019892:eIF-2 Kinase