title: Synergistic effects of eukaryotic co-expression plasmid-based STAT3-specific siRNA and LKB1 on ovarian cancer in vitro and in vivo.
abstract: The signal transducer and activator of transcription 3 (STAT3) are ideal targets for ovarian cancer. Previous studies showed that downregulation of STAT3 using specific short hairpin RNAs (shRNA) can significantly reduce ovarian tumor growth. However, RNA interference does not fully ablate target gene expression due to idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of STAT3-specific shRNA, we employed a combinatorial expression of STAT3-specific shRNA and liver kinase B1 (LKB1), a tumor suppressor. Thus, the LKB1 coding sequences and STAT3-specific shRNAs were constructed in a eukaryotic co-expression plasmid pCDNA3.1, and then transfected into ovarian cancer cells to evaluate the synergistic effects of this combination on anticancer activity and explore the relevant molecular mechanisms. Co-expression of STAT3‑specific siRNA and LKB1 (pSi-STAT3-LKB1) synergistically inhibited ovarian cancer cell growth, invasion and migration, induced cell apoptosis and arrested the cell cycle in vitro when compared with monotherapy. The results showed that the co-expression of plasmid pSi-STAT3-LKB1 inserted subcutaneously into ovarian tumor xenograft resulted in more significant inhibition of tumor growth. Further study showed that the synergistic anti-ovarian cancer effects of the co-expression of STAT3-specific siRNA and LKB1 may be associated with the upregulation of p-p53, p21 and downregulation of survivin, BCL-2 and cyclin D1. Results of the present study suggested that combined therapy with eukaryotic co-expression of the plasmid‑carrying STAT3-specific siRNA and LKB1 is a novel and efficient treatment strategy for human ovarian cancer.
authors.affiliation: Center for Reproductive Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Pan
authors.affiliation: Center for Reproductive Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Center for Reproductive Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Center for Reproductive Medicine, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
authors.forename: Ruizhi
authors.initials: R
authors.lastname: Liu
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D051379:Mice; D008819:Mice, Nude; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D010957:Plasmids / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D034741:RNA, Small Interfering / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics*; D023041:Xenograft Model Antitumor Assays
chemical_list: D034741:RNA, Small Interfering; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D000091162:AMP-Activated Protein Kinase Kinases