BACKGROUND/AIMS: Pancreatic cancer has the worst prognosis of any gastrointestinal cancer with a mortality rate approaching its incidence. Previous studies have indicated that GATA6 plays a key role in organ development and function, and that abnormal expression of GATA6 may induce tumorigenesis. Meanwhile, it has been reported that generation of reactive oxygen species contributes to carcinogenesis. In this study, we set out to study the role of GATA6 expression on proliferation and apoptosis of pancreatic cancer cells and the role of reactive oxygen species. METHODS: Four target miRNA sequences against GATA6 mRNA were synthesized and used to transfect SW1990 cells. Then, GATA6 expression in SW1990 cells was examined by western blot and quantative real-time polymerase chain reaction. Cell proliferation was examined by WST-8 and colony formation assay. Cell cycle progression and apoptosis were measured by flow cytometry. We also measured the generation of reactive oxygen species by immunofluorescence and flow cytometry. RESULTS: RNA interference against GATA6 successfully inhibited mRNA and protein expression of GATA6 in the SW1990 pancreatic cancer cell line. Silencing of GATA6 by RNA interference inhibited cell proliferation and increased apoptosis of SW1990, and enhanced the expression of reactive oxygen species. CONCLUSIONS: These results suggest that the RNA interference approach against GATA6 may be an effective therapeutic approach for treatment of pancreatic cancer.
BACKGROUND/AIMS: Pancreatic cancer has the worst prognosis of any gastrointestinal cancer with a mortality rate approaching its incidence. Previous studies have indicated that GATA6 plays a key role in organ development and function, and that abnormal expression of GATA6 may induce tumorigenesis. Meanwhile, it has been reported that generation of reactive oxygen species contributes to carcinogenesis. In this study, we set out to study the role of GATA6 expression on proliferation and apoptosis of pancreatic cancer cells and the role of reactive oxygen species. METHODS: Four target miRNA sequences against GATA6 mRNA were synthesized and used to transfect SW1990 cells. Then, GATA6 expression in SW1990 cells was examined by western blot and quantative real-time polymerase chain reaction. Cell proliferation was examined by WST-8 and colony formation assay. Cell cycle progression and apoptosis were measured by flow cytometry. We also measured the generation of reactive oxygen species by immunofluorescence and flow cytometry. RESULTS: RNA interference against GATA6 successfully inhibited mRNA and protein expression of GATA6 in the SW1990 pancreatic cancer cell line. Silencing of GATA6 by RNA interference inhibited cell proliferation and increased apoptosis of SW1990, and enhanced the expression of reactive oxygen species. CONCLUSIONS: These results suggest that the RNA interference approach against GATA6 may be an effective therapeutic approach for treatment of pancreatic cancer.
Authors: P M Lindholm; Y Soini; M Myllärniemi; S Knuutila; M Heikinheimo; V L Kinnula; K Salmenkivi Journal: J Clin Pathol Date: 2008-12-05 Impact factor: 3.411
Authors: Hanna Haveri; Mia Westerholm-Ormio; Katri Lindfors; Markku Mäki; Erkki Savilahti; Leif C Andersson; Markku Heikinheimo Journal: BMC Gastroenterol Date: 2008-04-11 Impact factor: 3.067
Authors: Eric A Collisson; Anguraj Sadanandam; Peter Olson; William J Gibb; Morgan Truitt; Shenda Gu; Janine Cooc; Jennifer Weinkle; Grace E Kim; Lakshmi Jakkula; Heidi S Feiler; Andrew H Ko; Adam B Olshen; Kathleen L Danenberg; Margaret A Tempero; Paul T Spellman; Douglas Hanahan; Joe W Gray Journal: Nat Med Date: 2011-04-03 Impact factor: 53.440