OncoTargets and Therapy (Feb 2020)

Downregulation of miR-486-5p Enhances the Anti-Tumor Effect of 5-Fluorouracil on Pancreatic Cancer Cells

  • Wang W,
  • Liu B,
  • Sun S,
  • Lan L,
  • Chen Y,
  • Han S,
  • Li X,
  • Li Z

Journal volume & issue
Vol. Volume 13
pp. 1649 – 1659

Abstract

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Wei Wang,1,* Bowei Liu,2,* Suofeng Sun,2 Ling Lan,2 Yu Chen,3 Shuangyin Han,2 Xiuling Li,2 Zhaoshen Li1 1Department of Gastroenterology, Changhai Hospital, Second Military Medical University/Naval Medical University, Shanghai 200433, People’s Republic of China; 2Department of Gastroenterology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, Zhengzhou, Henan 450003, People’s Republic of China; 3Department of Gastroenterology, Nanhai Hospital, Southern Medical University, Foshan, Guangdong 528200, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiuling LiDepartment of Gastroenterology, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, People’s Hospital of Henan University, No. 7 Weiwu Road, Jinshui District, Zhengzhou, Henan 450003, People’s Republic of ChinaTel +86-371-65580014Email [email protected]: 5-Fluorouracil (5-Fu) has been applied to treat pancreatic cancer, which is one of the most common types of digestive system tumors. Evidence has shown that miR-486-5p could promote the proliferation of pancreatic cancer cells. Therefore, this study aimed to investigate whether downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells.Methods: Cell Counting Kit 8 assay, flow cytometry and wound healing assays were used to detect proliferation, apoptosis and migration in PANC-1 cells. The expressions of Bcl-2, Bax, cleaved caspase 3, PTEN, p-Akt and p-ERK in PANC-1 cells were detected with Western blot assay.Results: In this study, the inhibitory effects of 5-Fu on the proliferation, migration and invasion of PANC-1 cells were significantly enhanced following transfection with miR-486-5p antagonist. In addition, downregulation of miR-486-5p markedly enhanced the pro-apoptosis effect of 5-Fu on PANC-1 cells. Moreover, bioinformatics analysis and luciferase reporter assay identified that PTEN was the directly binding target of miR-486-5p. Meanwhile, downregulation of miR-486-5p markedly enhanced the anti-tumor effect of 5-Fu in PANC-1 cells via upregulation of the level of PTEN, and downregulation of the expressions of p-ERK and p-Akt. In vivo experiments confirmed that knockdown of miR-486-5p could enhance the anti-tumor effect of 5-Fu in PANC-1 xenograft model.Conclusion: We found that the downregulation of miR-486-5p could enhance the anti-tumor effect of 5-Fu on pancreatic cancer cells. Therefore, miR-486-5p antagonist plus 5-Fu might be considered as a potential therapeutic strategy for the treatment of pancreatic cancer.Keywords: pancreatic cancer, 5-fluorouracil, miR-486-5p, PTEN, apoptosis

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