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Updated: Apr 5, 2026

Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Statins targeting mevalonate-geranylgeranyl diphosphate pathway inhibit proliferation in NK/T lymphoma by promoting

Yingjun Wang1, Mei Mei2, Jieting Wang1

  • 1Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.

Translational Oncology
|April 3, 2026
PubMed

Insights

Statins, specifically fluvastatin, suppress natural killer/T cell lymphoma (NKTCL) by activating pyroptosis, a programmed cell death pathway. This mechanism involves the mevalonate-geranyl pyrophosphate pathway, offering a new therapeutic strategy for NKTCL.

Area of Science:

  • Oncology
  • Immunology
  • Cell Biology

Background:

  • Pyroptosis, an inflammatory programmed cell death, is implicated in tumor development.
  • Statins exhibit known antitumor properties.
  • Natural killer/T cell lymphoma (NKTCL) is a significant clinical challenge.

Purpose of the Study:

  • To investigate the potential of statins to suppress NKTCL through pyroptosis.
  • To elucidate the underlying molecular mechanisms of statin-induced pyroptosis in NKTCL.
  • To evaluate the synergistic effects of statins with chemotherapy.

Main Methods:

  • In vitro cell culture (NKYS, YT cells) with statin treatment.
  • Cell viability, invasion, cell cycle, apoptosis, and pyroptosis assays (flow cytometry).
  • Protein expression analysis (Western blot, immunofluorescence) and electron microscopy; in vivo tumor models.

Main Results:

  • Fluvatatin (FLU) inhibited NKTCL cell proliferation and invasion in a dose-dependent manner.
  • FLU activated pyroptosis, evidenced by cell morphology changes, inflammasome formation, and increased Gasdermin D, cleaved caspase-1, and IL-1β/18.
  • Inhibition of pyroptosis or downstream pathways partially reversed FLU's effects; FLU and gemcitabine showed synergistic antitumor activity.

Conclusions:

  • Fluvatatin suppresses NKTCL growth by inducing pyroptosis via the mevalonate-geranyl pyrophosphate pathway.
  • Targeting pyroptosis presents a promising therapeutic avenue for NKTCL.
  • Combination therapy with statins and chemotherapy may enhance treatment efficacy.
Keywords:
Cancer therapyGeranylgeranyl diphosphateMevalonate pathwayNatural killer/T-cell lymphomaPyroptosisStatinSynergistic effect

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