Cisplatin promotes TNF-α autocrine to trigger RIP1/RIP3/MLKL-dependent necroptosis of human head and neck squamous cell carcinoma cells
10.12122/j.issn.1673-4254.2024.10.13
- VernacularTitle:顺铂诱导TNF-α自分泌引发头颈部鳞状癌细胞RIP1/RIP3/MLKL的坏死性凋亡
- Author:
Hongxiao WANG
1
;
Detao TAO
;
Junjie MA
;
Donglin ZHANG
;
Zuoyuan SHEN
;
Chao DENG
;
Jingping ZHOU
Author Information
1. 皖南医学院口腔医学院,安徽 芜湖 241002
- Keywords:
human head and neck squamous cell carcinoma;
cisplatin;
z-VAD-fmk;
necroptosis;
Nec-1
- From:
Journal of Southern Medical University
2024;44(10):1947-1954
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate whether cisplatin induces tumor necrosis factor-α(TNF-α)secretion in human head and neck squamous cell carcinoma(HNSCC)cells to trigger RIP1/RIP3/MLKL-dependent necroptosis of the cells.Methods HNSCC cell lines HN4 and SCC4 treated with cisplatin(CDDP)or the combined treatment with CDDP and z-VAD-fmk(a caspase inhibitor)or Nec-1(a necroptosis inhibitor)for 24 h were examined for changes in cell viability using CCK8 assay and expressions of caspase-8 and necroptosis pathway proteins(RIP1/RIP3/MLKL)using Western blotting.The changes in migration of the cells were assessed with cell scratch assay,and the expressions of epithelial-mesenchymal transition(EMT)marker proteins N-cadherin,vimentin,and E-cadherin as well as the expressions of NF-κB(p65)and TNF-α were detected with Western blotting.Results The IC50 of cisplatin was 10 μg/mL in HN4 cells and 15 μg/mL in SCC4 cells.Cisplatin treatment significantly decreased the expressions of caspase-8,N-cadherin and vimentin and increased the expressions of E-cadherin,the necroptosis pathway proteins(RIP1/RIP3/MLKL),TNF-α,and NF-κB(p65),and these changes were obviously inhibited by treatment with Nec-1.Cisplatin stimulation also significantly lowered migration of the cells,and this inhibitory effect was strongly attenuated by Nec-1 treatment.Conclusion Cisplatin activates nuclear factor-κB signaling in HNSCCs to promote TNF-α autocrine and induce RIP1/RIP3/MLKL-dependent necroptosis,thus leading to inhibition of cell proliferation.
