title: Lentiviral vector-mediated survivin shRNA delivery in gastric cancer cell lines significantly inhibits cell proliferation and tumor growth.
abstract: It has been well documented that survivin has multiple functions including cytoprotection, inhibition of cell death, and cell cycle regulation, particularly at the mitotic stage of the cell cycle, all of which favor cancer survival. Its expression in normal tissue is developmentally regulated, and any type of deregulation in survivin expression favors cancer survival. Gastric cancer is one of the most common malignancies and the second most common cause of cancer-related mortality worldwide. The molecular mechanisms involved in the transformation and progression of gastric cancer remain unclear. In the present study, we investigated the effect of lentiviral vector-mediated survivin shRNA delivery in gastric cancer cell lines. Lentiviral-mediated survivin shRNA was used to knock down survivin expression in gastric cancer cell lines SGC-7901, MGC-803 and MKN-28. The Τranswell chemotaxis and the CCK-8 assays were used to assess the migration and proliferation of the tumor cells, respectively. TUNEL assay was used to detect apoptosis. Quantitative real-time PCR and western blot analysis were used to quantify mRNA and protein levels, respectively. Our results demonstrated that lentiviral-mediated RNAi markedly suppressed the survivin expression in all three gastric cancer cell lines. Significant decrease in survivin mRNA and protein expression were detected in the gastric cancer cell lines stably transfected with the lentiviral survivin shRNA vector, and knockdown of survivin also significantly inhibited the proliferation and migration in the gastric cancer cells and tumorigenicity in a xenograft animal model. Our results indicated that aberrant high cytoplasmic survivin expression in gastric cancer cells is associated with increased proliferation index and tumor growth. In conclusion, our results suggest that lentiviral-mediated gene therapy has the potential to be developed into a novel therapeutic strategy for the treatment of gastric cancer.
authors.affiliation: Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Raees
authors.initials: R
authors.lastname: Habib
authors.affiliation: Department of Thoracic Surgery, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Javed
authors.initials: J
authors.lastname: Akhtar
authors.affiliation: Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Taqi
authors.affiliation: Department of Nephrology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Che
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Gastroenterology, Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, P.R. China.
authors.forename: Chunqing
authors.initials: C
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D016086:Lentivirus / Q000235:genetics; D051379:Mice; D034741:RNA, Small Interfering / Q000235:genetics; D013274:Stomach Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D000077022:Survivin; D023041:Xenograft Model Antitumor Assays
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D034741:RNA, Small Interfering; D000077022:Survivin