1. Academic Validation
  2. Mitochondrial division inhibitor (mdivi-1) inhibits proliferation and epithelial-mesenchymal transition via the NF-κB pathway in thyroid cancer cells

Mitochondrial division inhibitor (mdivi-1) inhibits proliferation and epithelial-mesenchymal transition via the NF-κB pathway in thyroid cancer cells

  • Toxicol In Vitro. 2023 Jan 5;105552. doi: 10.1016/j.tiv.2023.105552.
Lin Zhang 1 Lei Sun 1 Lirong Wang 1 Juan Wang 1 Dan Wang 1 Jue Jiang 1 Jinhui Zhang 1 Qi Zhou 2
Affiliations

Affiliations

  • 1 Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, PR China.
  • 2 Department of Ultrasound, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710004, PR China. Electronic address: zhouqi17788979083@163.com.
Abstract

Excessively fragmented mitochondria have been reported in thyroid Cancer (TC). Mitochondrial division inhibitor (mdivi-1), a putative inhibitor of dynamin-related protein 1 (Drp1), prevents mitochondrial fission and thereby restricts cell proliferation across several types of primary Cancer. However, the role of mdivi-1 on TC has not been sufficiently studied. This research is intended to explore the therapeutic effect of mdivi-1 in TC cells. Results demonstrated that highly invasive TC cells displayed excessive mitochondrial fission with more fragmented mitochondria. Treatment with mdivi-1 inhibited mitochondrial fission in 8505C cells as indicated by transmission electron microscope (TEM). It also impaired the proliferation and increased Apoptosis in 8505C and K1 cells as shown by plate cloning assay, cell viability assay, and Apoptosis assay. Mdivi-1 treatment also attenuated migratory and invasive abilities in 8505C and K1 cells as shown by the transwell assay and wound healing assay. And we noticed the same inhibition of mdivi-1 in cell migration and cell viability after the knockdown of Drp1 in 8505C cells. This demonstrated that mdivi-1 exerts an anti-tumor effect independently of Drp1 in 8505C cells. Moreover, mdivi-1 treatment reversed epithelial-mesenchymal transition (EMT) by inhibiting the NF-κB pathway in 8505C cells. The present findings demonstrate that mdivi-1 has a therapeutic role in thyroid carcinoma.

Keywords

Drp1; Epithelial-mesenchymal transition; Mdivi-1; Mitochondrial fission; NF-κB pathway; Thyroid cancer.

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