2. Academic Validation
  3. Ibuprofen inhibits anaplastic thyroid cells in vivo and in vitro by triggering NLRP3-ASC-GSDMD-dependent pyroptosis

Ibuprofen inhibits anaplastic thyroid cells in vivo and in vitro by triggering NLRP3-ASC-GSDMD-dependent pyroptosis

  • Inflammopharmacology. 2023 Nov 24. doi: 10.1007/s10787-023-01379-7.
Haohao Guo 1 2 3,  Runsheng Ma 1,  Yifei Zhang 1 2 3,  Keyu Yin 4,  Gongbo Du 1,  Fanxiang Yin 5,  Hongqiang Li 1,  Ziyang Wang 1,  Detao Yin 6 7 8
Affiliations

Affiliations

  • 1 Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 2 Engineering Research Center of Multidisciplinary Diagnosis and Treatment of Thyroid Cancer of Henan Province, Zhengzhou, 450052, Henan, China.
  • 3 Key Medicine Laboratory of Thyroid Cancer of Henan Province, Zhengzhou, 450052, Henan, China.
  • 4 School of Basic Medical Sciences, Lanzhou University, Lanzhou, 730000, Gansu, China.
  • 5 Translational Medical Center, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China.
  • 6 Department of Thyroid Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, Henan, China. detaoyin@zzu.edu.cn.
  • 7 Engineering Research Center of Multidisciplinary Diagnosis and Treatment of Thyroid Cancer of Henan Province, Zhengzhou, 450052, Henan, China. detaoyin@zzu.edu.cn.
  • 8 Key Medicine Laboratory of Thyroid Cancer of Henan Province, Zhengzhou, 450052, Henan, China. detaoyin@zzu.edu.cn.
PMID: 37999895 DOI: 10.1007/s10787-023-01379-7
Abstract

Pyroptosis is a novel type of proinflammatory programmed cell death that is associated with inflammation, immunity, and Cancer. Anaplastic thyroid carcinoma (ATC) has a high fatality rate, and there is no effective or standard treatment. The disease progresses rapidly and these tumors can invade the trachea and esophagus, leading to breathing and swallowing difficulties. Hence, new treatment methods are greatly needed. Ibuprofen is a common drug that can exert antitumor effects in some cancers. In this study, we demonstrated in vitro and in vivo that ibuprofen can induce ATC Pyroptosis. Hence, we treated C643 and OCUT-2C ATC cells with ibuprofen and found that several dying cells presented the characteristic morphological features of Pyroptosis, such as bubble-like swelling and membrane rupture, accompanied by activation of ASC and NLRP3 and cleavage of GSDMD. Along with the increased release of LDH, ibuprofen treatment promoted Apoptosis and inhibited viability, invasion, and migration. However, overexpression of GSDMD significantly inhibited ibuprofen-induced Pyroptosis. In vivo, research has demonstrated that thyroid tumor growth in nude mice can be suppressed by ibuprofen-induced Pyroptosis in a dose-dependent manner. In this research, we explored a new mechanism by which ibuprofen inhibits ATC growth and progression and highlighted its promise as a therapeutic agent for ATC.

Keywords

Anaplastic thyroid cancer; Ibuprofen; Inflammation; Pyroptosis.

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