机构：[1]Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Soochow 215004, China,[2]Department of Orthopaedics, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong 226001, China[3]Department of Dermatology, Affiliated Hospital of Nantong University, Nantong 226001, China
Simultaneous silencing of multiple upregulated genes is an attractive and viable treatment strategy for many incurable diseases including cancer. Herein we used a dual gene-targeted siRNA conjugate composed of VEGF and Survivin siRNA sequences in the same backbone to inhibit proliferation and angiogenesis in two human osteosarcoma cell lines. We synthesized siRNA sequences targeting the VEGF and Survivin genes individually (VEGF siRNA and Survivin siRNA) or simultaneously (one-chain-double-target siRNA: dual siRNA). VEGF and Survivin mRNA and protein expression levels in human osteosarcoma MG-63 and Saos-2 cells were detected by qRT-PCR and western blot analysis. VEGF and Survivin protein location and expression were evaluated by immunohistochemistry and immunofluorescence staining. MG-63 and Saos-2 cell migration, proliferation, apoptosis, and angiogenesis were detected by scratch test, MTT assay, flow cytometry, and capillary tube assay respectively. The dual siRNA induced similar downregulation of VEGF and Survivin mRNA and protein levels, compared with VEGF siRNA or Survivin siRNA alone. The dual siRNA caused greater suppression of MG-63 and Saos-2 cell migration, proliferation and angiogenesis, and promoted more cell apoptosis than VEGF siRNA or Survivin siRNA alone, suggesting that the effects of the dual siRNA on inhibiting cell proliferation, migration, and angiogenesis and promoting apoptosis were superior to those of the single-target siRNAs. Simultaneous silencing of VEGF and Survivin using the dual siRNA may be an advantageous alternative for the development of therapeutic strategies against human osteosarcoma.
基金：
This work was supported by the grant from the Second Affiliated
Hospital of Soochow University Preponderant Clinic Discipline
Group Project (No. XKQ2015003).
第一作者机构：[1]Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Soochow 215004, China,[2]Department of Orthopaedics, Affiliated Maternity and Child Health Care Hospital of Nantong University, Nantong 226001, China
通讯作者：
通讯机构：[1]Department of Orthopaedics, The Second Affiliated Hospital of Soochow University, Soochow 215004, China,
推荐引用方式(GB/T 7714)：
Junquan Gu,Zhoujing Ji,Dong Li,et al.Proliferation inhibition and apoptosis promotion by dual silencing of VEGF and Survivin in human osteosarcoma[J].ACTA BIOCHIMICA ET BIOPHYSICA SINICA.2019,51(1):59-67.doi:10.1093/abbs/gmy146.
APA：
Junquan Gu,Zhoujing Ji,Dong Li&Qirong Dong.(2019).Proliferation inhibition and apoptosis promotion by dual silencing of VEGF and Survivin in human osteosarcoma.ACTA BIOCHIMICA ET BIOPHYSICA SINICA,51,(1)
MLA：
Junquan Gu,et al."Proliferation inhibition and apoptosis promotion by dual silencing of VEGF and Survivin in human osteosarcoma".ACTA BIOCHIMICA ET BIOPHYSICA SINICA 51..1(2019):59-67
