Metformin suppresses the invasive ability of pancreatic cancer cells by blocking autocrine TGF‑β1 signaling

  • Authors:
    • Wanxing Duan
    • Weikun Qian
    • Cancan Zhou
    • Junyu Cao
    • Tao Qin
    • Ying Xiao
    • Liang Cheng
    • Jie Li
    • Ke Chen
    • Xuqi Li
    • Jiguang Ma
    • Qingyong Ma
  • View Affiliations

  • Published online on: June 22, 2018     https://doi.org/10.3892/or.2018.6518
  • Pages: 1495-1502
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Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a highly invasive neoplasm with a 5‑year survival rate of <8%. Metformin, the most widely used antidiabetic drug in the world, has been shown to exert anticancer activities in epidemiological and animal studies. Our previous studies revealed that metformin suppressed desmoplasia in PDAC by reducing TGF‑β1 production in cancer cells. The aim of the present study was to investigate the effects of metformin on invasion and epithelial‑mesenchymal transition (EMT) in pancreatic cancer and to reveal the underlying mechanisms. In the present study, we revealed that metformin suppressed migration, invasion and EMT changes in pancreatic cancer cells. Furthermore, metformin reduced TGF‑β1 production and Smad2/3 phosphorylation in pancreatic cancer cells. In addition, treatment with recombinant TGF‑β1 recovered the metformin‑mediated invasion inhibition and EMT changes. Treatment with metformin also suppressed tumor growth, invasion and EMT in LSL‑KrasG12D/+, Trp53fl/+and Pdx1‑Cre (KPC) transgenic mice that harbor spontaneous pancreatic cancer. Collectively, our study revealed a new possible mechanism for the antitumor effects of metformin via autocrine TGF‑β1/Smad2/3 signaling in PDAC.
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September-2018
Volume 40 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Duan W, Qian W, Zhou C, Cao J, Qin T, Xiao Y, Cheng L, Li J, Chen K, Li X, Li X, et al: Metformin suppresses the invasive ability of pancreatic cancer cells by blocking autocrine TGF‑β1 signaling. Oncol Rep 40: 1495-1502, 2018
APA
Duan, W., Qian, W., Zhou, C., Cao, J., Qin, T., Xiao, Y. ... Ma, Q. (2018). Metformin suppresses the invasive ability of pancreatic cancer cells by blocking autocrine TGF‑β1 signaling. Oncology Reports, 40, 1495-1502. https://doi.org/10.3892/or.2018.6518
MLA
Duan, W., Qian, W., Zhou, C., Cao, J., Qin, T., Xiao, Y., Cheng, L., Li, J., Chen, K., Li, X., Ma, J., Ma, Q."Metformin suppresses the invasive ability of pancreatic cancer cells by blocking autocrine TGF‑β1 signaling". Oncology Reports 40.3 (2018): 1495-1502.
Chicago
Duan, W., Qian, W., Zhou, C., Cao, J., Qin, T., Xiao, Y., Cheng, L., Li, J., Chen, K., Li, X., Ma, J., Ma, Q."Metformin suppresses the invasive ability of pancreatic cancer cells by blocking autocrine TGF‑β1 signaling". Oncology Reports 40, no. 3 (2018): 1495-1502. https://doi.org/10.3892/or.2018.6518