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Salidroside regulates tumor microenvironment of non-small cell lung cancer via Hsp70/Stub1/Foxp3 pathway in Tregs

Zexin Wen1, Tong Liu1,2, Yanli Zhang1

  • 1Department of Medicine, Xizang Minzu University, Xianyang, Shaanxi, China.

BMC Cancer
|August 1, 2023
PubMed
Abstract

Insights

Salidroside (SAL) suppresses non-small cell lung cancer growth by targeting regulatory T cells (Tregs). This novel mechanism involves the Hsp70/Stub1/Foxp3 pathway, offering a new avenue for antitumor therapy.

Area of Science:

  • Immunology
  • Oncology
  • Pharmacology

Background:

  • Non-small cell lung cancer (NSCLC) presents treatment challenges due to immune evasion.
  • Salidroside (SAL), a traditional Chinese medicine extract, shows potential antitumor effects.
  • The precise mechanism of SAL in modulating the NSCLC immunological microenvironment remains unclear.

Purpose of the Study:

  • To elucidate the mechanism by which Salidroside (SAL) regulates the immune microenvironment in non-small cell lung cancer (NSCLC).
  • To investigate the effect of SAL on regulatory T cells (Tregs) and their associated molecular pathways.
  • To explore a novel antitumor mechanism of SAL for NSCLC treatment.

Main Methods:

  • Established a Lewis lung cancer (3LL) mouse model in C57BL/6 mice for SAL treatment studies.
  • Analyzed tumor-infiltrating T cell subsets, including Tregs, using flow cytometry.
  • Utilized network pharmacology, molecular docking, flow cytometry, and confocal microscopy to identify SAL targets and confirm molecular interactions.
  • Employed an Hsp70 inhibitor to validate the role of the Hsp70/Stub1/Foxp3 pathway.

Main Results:

  • SAL treatment reduced tumor cell growth by decreasing the percentage of tumor-infiltrated CD4+Foxp3+ T cells (Tregs).
  • SAL downregulated Foxp3 expression in Tregs while upregulating Stub1 and Hsp70 expression.
  • Inhibition of Hsp70 reversed SAL's effect on Foxp3 and disrupted Stub1-Foxp3 nuclear colocalization.

Conclusions:

  • SAL inhibits NSCLC tumor growth by suppressing Treg function via the Hsp70/Stub1/Foxp3 pathway.
  • This study reveals a novel mechanism for SAL's antitumor activity in NSCLC.
  • SAL represents a potential therapeutic agent for NSCLC by modulating the tumor immune microenvironment.
Keywords:
Non-small cell lung cancerSalidrosideStub1TregTumor microenvironment

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