Resveratrol reverses the cadmium-promoted migration, invasion, and epithelial-mesenchymal transition procession by regulating the expression of ZEB1

Hum Exp Toxicol. 2021 Dec;40(12_suppl):S331-S338. doi: 10.1177/09603271211041678. Epub 2021 Sep 7.

Abstract

Resveratrol has been reported as an ideal medicine in the treatment of colorectal cancer. Meanwhile, cadmium could affect the occurrence and development of tumors in various ways. Epithelial-mesenchymal transition is a major progress regulated with colorectal cancer (CRC). We aimed to determine the effect and mechanism of resveratrol on the Cd-promoted EMT in CRC cells. First, we investigated the migration and invasion of CRC cells with or without the treatment of different concentrations of Cd in vitro by the transwell assay. Second, Western blot and RT-qPCR assay were used to detect the expressions of EMT-related markers (ZEB1, vimentin, E-cadherin, and N-cadherin) in Cd-exposed CRC cells. Subsequently, after treating with different concentrations of resveratrol, the migration and invasion of Cd-exposed CRC cells were detected again, as well as the expressions of EMT-related markers. Moreover, m6A-related RNAs in Cd-exposed CRC cells after treating with resveratrol were immunoprecipitated and validated by Me-RIP and RT-qPCR. These indicated that Cd promoted the migration and invasion of CRC cells. In addition, Cd up-regulated the expressions of N-cadherin, vimentin, and ZEB1, while it down-regulated that of E-cadherin in CRC cells. Resveratrol could reverse the Cd-promoted migration, invasion, and EMT procession by regulating the expression of ZEB1.

Keywords: N6-methyladenosine; Resveratrol; cadmium; colorectal cancer cells; epithelial–mesenchymal transition.

MeSH terms

  • Cadmium / toxicity*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology
  • Down-Regulation / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Humans
  • Neoplasm Metastasis / prevention & control*
  • Resveratrol / pharmacology*
  • Up-Regulation / drug effects
  • Zinc Finger E-box-Binding Homeobox 1 / metabolism*

Substances

  • ZEB1 protein, human
  • Zinc Finger E-box-Binding Homeobox 1
  • Cadmium
  • Resveratrol