Artesunate inhibits epithelial-mesenchymal transition in non-small-cell lung cancer (NSCLC) cells by down-regulating the expression of BTBD7

Bioengineered. 2020 Dec;11(1):1197-1207. doi: 10.1080/21655979.2020.1834727.

Abstract

In recent years, more and more studies have shown that antiparasitic drugs can affect a variety of biological processes of tumor cells and exhibit a potential anti-tumor activity. Although artesunate (ART), a strong bioactive derivative of artemisinin and widely used clinically against malaria, was found to have an inhibitory effect on tumor cells, it is still unclear whether ART could regulate the tumor malignancy of non-small-cell lung cancer (NSCLC) cells. In this study, we aimed to investigate the effect of ART on migration capacities in NSCLC cell lines of A549 and H1975. Cell migration capacity was remarkably inhibited by ART treatment. The expression of epithelial marker E-cadherin was upregulated, while mesenchymal markers (N-cadherin, vimentin and FN1) were inhibited by ART in both protein and mRNA levels in A549 and H1975 cells, indicating ART could suppress the epidermal interstitial transformation (EMT) of NSCLC cells. Meanwhile, BTBD7 was found highly expressed in tumor tissues of NSCLC patient and associated with poor prognosis. The anti-migration activity of ART was found to be mediated by the inhibition of BTBD7 mRNA expression and was reversed when the cells were transiently transfected with the BTBD7 overexpression plasmid. Our study demonstrated the potent anti-migratory activity of ART, thereby presenting it as a new candidate for clinical therapy in NSCLC.

Keywords: BTBD7; EMT; Non-small-cell lung cancer (NSCLC); artesunate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A549 Cells
  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Artesunate / pharmacology
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / pathology*
  • Cell Line
  • Cell Movement / drug effects
  • Epithelial-Mesenchymal Transition / genetics
  • Epithelial-Mesenchymal Transition / physiology*
  • Humans
  • RNA, Messenger / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • BTBD7 protein, human
  • RNA, Messenger
  • Artesunate

Grants and funding

This work was supported by the National Natural Science Foundation of China [grant number 81972190 and 81802457] and Natural Science Foundation of Chongqing [cstc2017jcyjAX0048.