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Knockdown of SLC39A4 Expression Inhibits the Proliferation and Motility of Gallbladder Cancer Cells and Tumor Formation in Nude Mice

Authors Li M, Fan K, Zheng B, Zekria D, Suo T, Liu H, Shen S, Liu H, Ni X

Received 6 October 2020

Accepted for publication 1 February 2021

Published 8 March 2021 Volume 2021:13 Pages 2235—2246


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Dr Eileen O'Reilly

Min Li,1,* Kun Fan,1,* Bohao Zheng,1,* David Zekria,2 Tao Suo,1 Han Liu,1 Sheng Shen,1 Houbao Liu,1 Xiaoling Ni1

1Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China; 2Department of Radiology, Leicester Royal Infirmary, Leicester, LE1 5WW, UK

*These authors contributed equally to this work

Correspondence: Xiaoling Ni; Houbao Liu
Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of China
Tel +86 21 64041998; +86 21 64041997
Email [email protected]; [email protected]

Purpose: Gallbladder cancer (GBC) is a common malignancy of the biliary tract and is characterized by rapid progression and early metastasis. Elucidating the molecular mechanisms of GBC could help to develop better treatment strategies.
Materials and Methods: Human GBC cell lines (GBC-SD and NOZ) were applied to determine the capacity of the proliferation and migration of cells using the MTT assay, colony formation, wound-healing assay as well as the Transwell™ assay. A nude xenograft was used to evaluate tumor growth in vivo.
Results: Using two types of GBC cell lines, we found that absence of solute carrier family (SLC) 39A4 (which encodes the zinc transporter ZRT/IRT-like protein [ZIP]4), could suppress the proliferation and migration of cells. Additionally, absence of ZIP4 could impair growth of xenografts in nude mice. While, over-expression of SLC39A4 could promote the GBC cell proliferation and migration, and inhibit apoptosis. We revealed that SLC39A4 might affect GBC progression by modulating the signaling pathways responsible for the survival, energy supply and metastasis of cells, and indicated that SLC39A4 could serve as a novel therapeutic target for GBC.
Conclusion: SLC39A4 promoted the viability and motility of GBC cells, and tumor formation in nude mice. We demonstrated an oncogenic potential for SLC39A4.

Keywords: gallbladder cancer, SLC39A4 (ZIP4), proliferation, migration, potential therapeutic target

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