The anti-alcohol dependency drug disulfiram inhibits the viability and progression of gastric cancer cells by regulating the Wnt and NF-κB pathways

Author:

Zhang Jun12ORCID,Pu Ke12,Bai Suyang12,Peng Yukui12ORCID,Li Fan12,Ji Rui12,Guo Qinghong12,Sun Weiming3,Wang Yuping12

Affiliation:

1. Department of Gastroenterology, The First Hospital of Lanzhou University, Lanzhou, China

2. Key Laboratory for Gastrointestinal Diseases of Gansu Province, Lanzhou University, Lanzhou, China

3. Department of Endocrinology, The First Hospital of Lanzhou University, Lanzhou, China

Abstract

Objective Disulfiram is commonly used for alcohol abuse; however, recent studies have revealed its potential as an anti-cancer treatment. This study investigated the effects of disulfiram on gastric cancer and its underlying mechanisms of action. Methods The gastric cancer cell lines MKN-45 and SGC-7901 were used for all experiments. Cell proliferation was investigated using cell counting kit-8, cell migration and invasion were examined using Transwell assays, the proliferation and metastasis related proteins PCNA and MMP-2, respectively, were detected by ELISA. To explore the underlying molecular mechanisms, we also examined levels of proteins involved in the Wnt and NF-κB pathways by ELISA. Results Disulfiram significantly inhibited the proliferation, migration, and invasion of gastric cancer cells and decreased PCNA and MMP-2 levels. Additionally, disulfiram-treated MKN-45 and SGC-7901 cells showed reduced expression of Wnt, β-catenin, and NF-κB. Conclusion Disulfiram regulates the Wnt and NF-κB pathways, and thus could be a potential treatment for managing gastric cancer.

Funder

National Natural Science Foundation of China

National Key Research and Development Program of China

Open Fund of State Key Laboratory of Cancer Biology, China

Publisher

SAGE Publications

Subject

Biochemistry, medical,Cell Biology,Biochemistry,General Medicine

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