1. Academic Validation
  2. Low-Dose Albendazole Inhibits Epithelial-Mesenchymal Transition of Melanoma Cells by Enhancing Phosphorylated GSK-3 β/Tyr216 Accumulation

Low-Dose Albendazole Inhibits Epithelial-Mesenchymal Transition of Melanoma Cells by Enhancing Phosphorylated GSK-3 β/Tyr216 Accumulation

  • J Oncol. 2021 Dec 20;2021:4475192. doi: 10.1155/2021/4475192.
Zhiqiang He 1 Shun Lei 2 Fucheng Liang 1 Liuchang Tan 1 Weinan Zhang 1 Luoyingzi Xie 3 Hong Zheng 4 Yuangang Lu 1
Affiliations

Affiliations

  • 1 Department of Plastic & Cosmetic Surgery, Army Medical Center of PLA, Amy Medical University, Chongqing 400042, China.
  • 2 Department of Oncology and Southwest Cancer Center, Southwest Hospital, Army Medical University, Chongqing 400038, China.
  • 3 The Institute of Immunology, Army Medical University, Chongqing 400038, China.
  • 4 Department of Thoracic Surgery, Xinqiao Hospital, Amy Medical University, Chongqing 400037, China.
Abstract

Albendazole (ABZ) is an effective broad-spectrum anthelmintic agent that has been widely used for humans and Animals. Previous studies have reported that ABZ exhibits antitumor effects against melanoma and other different Cancer types; however, it is unknown whether ABZ exerts the inhibitory effect against melanoma metastasis. In this study, we aimed to investigate the inhibitory effect of ABZ on melanoma cells. Through in vitro studies, we discovered that low-dose ABZ treatment significantly inhibited the migration and invasion, but not the proliferation, of A375 and B16-F10 cells in a dose-dependent manner. Further analysis revealed that ABZ treatment reduced the expression level of snail family transcriptional repressor 1 (Snail) in the cytoplasm and nucleus by decreasing the levels of phosphorylated Akt (pAKT) Ser473/GSK-3β (pGSK-3β) Ser9 and increasing pGSK-3β/Tyr216, resulting in a significant upregulation of E-cadherin and downregulation of N-Cadherin and ultimately reversing the epithelial-mesenchymal transition (EMT) process of melanoma cells. In contrast, the continuous activation of Akt via transfected plasmids elevated the protein levels of pAKT Ser473/pGSK-3β Ser9 and Snail and antagonized the inhibitory action of ABZ. We also confirmed that ABZ treatment effectively inhibited the lung metastasis of melanoma in nude mice in vivo. Subsequent immunohistochemical analysis verified the decreased pAKT Ser473/pGSK-3β Ser9 and increased pGSK-3β/Tyr216 levels in ABZ-treated subcutaneous tumors. Therefore, our findings demonstrate that ABZ treatment can suppress the EMT progress of melanoma by increasing the pGSK-3β/Tyr216-mediated degradation of Snail, which may be used as a potential treatment strategy for metastatic melanoma.

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