Regulation of ABCG2 expression by Wnt5a through FZD7 in human pancreatic cancer cells

Zhang,Zhongbo; Gao,Shuang; Xu,Yuanhong; Zhao,Chenghai

doi:10.3892/mmr.2020.11690

Regulation of ABCG2 expression by Wnt5a through FZD7 in human pancreatic cancer cells

Authors:
- Zhongbo Zhang
- Shuang Gao
- Yuanhong Xu
- Chenghai Zhao
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Affiliations: Department of Pancreatic and Biliary Surgery, The First Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Bioengineering, College of Life Science, North China University of Science and Technology, Tangshan, Hebei 063000, P.R. China, Department of Pathophysiology, Basic Medical College, China Medical University, Shenyang, Liaoning 110001, P.R. China
Published online on: November 16, 2020 https://doi.org/10.3892/mmr.2020.11690
Article Number: 52
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

ATP‑binding cassette subfamily G member 2 (ABCG2), a member of the ABC transporter superfamily, has been implicated in the development of chemotherapeutic drug resistance in cancer cells. However, the regulators of ABCG2 expression and their roles in anticancer drug resistance have not been fully characterized, especially in the context of pancreatic cancer. The aim of the present study was to investigate whether ABCG2 contributed to drug resistance in pancreatic cancer and to elucidate its regulatory molecular pathways. Using immunohistochemical analysis of pancreatic ductal adenocarcinoma and adjacent healthy tissue samples, the present study identified a positive correlation between ABCG2 and Wnt5a, a member of the Wnt family of secreted proteins. It was also determined that treatment with recombinant human Wnt5a protein could upregulate the expression of ABCG2 in the Capan‑2 human pancreatic cancer cell line and enhance its resistance to gemcitabine. The upregulation of ABCG2 by Wnt5a was inhibited by small interfering RNA silencing of Frizzled class receptor 7 (FZD7) or by FZD7 inhibitors. Moreover, both FZD7 silencing or inhibition of its function attenuated gemcitabine resistance induced by Wnt5a in Capan‑2 cells. Therefore, the present findings suggested that Wnt5a and FZD7 acted as upstream regulators of ABCG2 expression and that FZD7 may be an essential factor for Wnt5a‑induced gemcitabine resistance in pancreatic cancer cells.

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