Cancer Management and Research (Mar 2021)

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

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

Journal volume & issue
Vol. Volume 13
pp. 2235 – 2246

Abstract

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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 workCorrespondence: Xiaoling Ni; Houbao LiuDepartment of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, 200032, People’s Republic of ChinaTel +86 21 64041998; +86 21 64041997Email [email protected]; [email protected]: 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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