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Development of a 68Gallium-Labeled D-Peptide PET Tracer for Imaging Programmed Death-Ligand 1 Expression
Published on: February 3, 2023
Novel thioredoxin reductase inhibitor butaselen inhibits tumorigenesis by down-regulating programmed death-ligand 1
Qiao Zou1,2, Yi-Fan Chen1,2, Xiao-Qing Zheng1,2
1State Key Laboratory of Natural and Biomimetic Drugs, Beijing 100191, China.
Abstract:
The thioredoxin system plays a role in a variety of physiological functions, including cell growth, differentiation, apoptosis, tumorigenesis, and immunity. We previously confirmed that butaselen (BS), a novel thioredoxin reductase inhibitor, can inhibit the growth of various human cancer cell lines, yet the underlying mechanism remains elusive. In this study, we investigated the anti-tumor effect of BS in vivo through regulating the immune system of KM mice. We found that BS inhibits tumor proliferation by promoting the activation of splenic lymphocytes in mice. BS can elevate the percentage of CD4-CD8+ T lymphocytes and the secretion of downstream cytokines in mice via down-regulating the expression of programmed death-ligand 1 (PD-L1) on the tumor cells' surface in vivo. Further study in HepG2 and BEL-7402 cells showed that decrease of PD-L1 level after BS treatment was achieved by inhibiting signal transducer and activator of transcription 3 (STAT3) phosphorylation. Taken together, our results suggest that BS has a role in promoting the immune response by reducing PD-L1 expression via the STAT3 pathway, and subsequently suppresses tumorigenesis.
Insights
Butaselen (BS) inhibits tumor growth by activating immune cells. This thioredoxin reductase inhibitor reduces PD-L1 expression via the STAT3 pathway, enhancing anti-tumor immunity.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- The thioredoxin system is vital for cell functions, including immunity and cancer.
- Butaselen (BS), a thioredoxin reductase inhibitor, shows anti-cancer potential, but its mechanism is unclear.
Purpose of the Study:
- To investigate the in vivo anti-tumor effects of butaselen (BS) by examining its impact on the immune system.
- To elucidate the molecular mechanisms underlying BS's anti-tumor activity.
Main Methods:
- In vivo studies using KM mice to assess BS's effect on tumor proliferation and immune cell activation.
- Flow cytometry to analyze T lymphocyte populations (CD4-, CD8+).
- Analysis of cytokine secretion and programmed death-ligand 1 (PD-L1) expression.
- In vitro studies on HepG2 and BEL-7402 cells to investigate the STAT3 signaling pathway.
Main Results:
- BS inhibited tumor proliferation in mice by activating splenic lymphocytes.
- BS treatment increased CD4-CD8+ T lymphocytes and cytokine secretion.
- BS down-regulated PD-L1 expression on tumor cells.
- BS inhibited STAT3 phosphorylation, leading to decreased PD-L1 levels in cancer cells.
Conclusions:
- Butaselen (BS) exhibits anti-tumor effects by modulating the immune response.
- BS promotes anti-tumor immunity through the down-regulation of PD-L1 via the STAT3 pathway.
- BS represents a potential therapeutic agent for cancer by enhancing immune-mediated tumor suppression.
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