Abstract
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.
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Acknowledgments
The authors thank Wanling Yang (Hong Kong University, China) for his helpful discussion of the manuscript and the Lab of Target Therapy of Sun Yat-sen Memorial Hospital for the technical assistance. This research was supported in part by a grant from the Natural Science Foundation of Guangdong Province (No. 815100890100013, 04009381) and Medical Scientific Research Foundation of Guangdong Province (No. B2009066).
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Wen-Bo Chen and Feng-Ting Huang contributed equally to this work.
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Chen, WB., Huang, FT., Zhuang, YY. et al. Silencing of GATA6 Suppresses SW1990 Pancreatic Cancer Cell Growth In Vitro and Up-Regulates Reactive Oxygen Species. Dig Dis Sci 58, 2518–2527 (2013). https://doi.org/10.1007/s10620-013-2752-4
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DOI: https://doi.org/10.1007/s10620-013-2752-4