Back to Journals » OncoTargets and Therapy » Volume 9

Interleukin-32α inactivates JAK2/STAT3 signaling and reverses interleukin-6-induced epithelial–mesenchymal transition, invasion, and metastasis in pancreatic cancer cells

Authors Chen J, Wang S, Su J, Chu G, You H, Chen Z, Sun H, Chen B, Zhou M

Received 4 January 2016

Accepted for publication 20 April 2016

Published 11 July 2016 Volume 2016:9 Pages 4225—4237

DOI https://doi.org/10.2147/OTT.S103581

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Ram Prasad

Peer reviewer comments 3

Editor who approved publication: Dr Faris Farassati


Jingfeng Chen,1,2,* Silu Wang,1,* Jiadong Su,1 Guanyu Chu,1 Heyi You,1 Zongjing Chen,1 Hongwei Sun,1 Bicheng Chen,1,3 Mengtao Zhou1

1Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 2Department of Surgery, The Sixth Affiliated Hospital of Wenzhou Medical University, Lishui, 3Zhejiang Provincial Top Key Discipline in Surgery, Wenzhou Key Laboratory of Surgery, Department of Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China

*These authors contributed equally to this work

Abstract: Interleukin (IL)-32 is a newly discovered cytokine that has multifaceted roles in inflammatory bowel disease, cancer, and autoimmune diseases and participates in cell apoptosis, cancer cell growth inhibition, accentuation of inflammation, and angiogenesis. Here, we investigated the potential effects of IL-32α on epithelial–mesenchymal transition, metastasis, and invasion, and the JAK2/STAT3 signaling pathway in pancreatic cancer cells. The human pancreatic cancer cell lines PANC-1 and SW1990 were used. Epithelial–mesenchymal transition-related markers, including E-cadherin, N-cadherin, Vimentin, Snail, and Zeb1, as well as extracellular matrix metalloproteinases (MMPs), including MMP2, MMP7, and MMP9, were detected by immunofluorescence, Western blotting, and real-time polymerase chain reaction. The activation of JAK2/STAT3 signaling proteins was detected by Western blotting. Wound healing assays, real-time polymerase chain reaction, and Western blotting were performed to assess cell migration and invasion. The effects of IL-32α on the IL-6-induced activation of JAK2/STAT3 were also evaluated. In vitro, we found that IL-32α inhibits the expressions of the related markers N-cadherin, Vimentin, Snail, and Zeb1, as well as JAK2/STAT3 proteins, in a dose-dependent manner in pancreatic cancer cell lines. Furthermore, E-cadherin expression was increased significantly after IL-32α treatment. IL-32α downregulated the expression of MMPs, including MMP2, MMP7, and MMP9, and decreased wound healing in pancreatic cancer cells. These consistent changes were also found in IL-6-induced pancreatic cancer cells following IL-32α treatment. This study showed that reversion of epithelial–mesenchymal transition, inhibition of invasiveness and metastasis, and activation of the JAK2/STAT3 signaling pathway could be achieved through the application of exogenous IL-32α.

Keywords: EMT, MMPs, IL-32α, JAK2, STAT3

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]