CTH Promotes Liver Cancer Progression and Exploratory Evaluation Supports Enhanced Antitumor Activity of PPG Plus GPC3 CAR-T Cells.

Authors

Yuxin Guo, Man Yu, Xilin Zhu, Wei Li, Ying Liu, Xiaopan Wu

Published in

Journal of immunology research. Volume 2026. Issue 1. Pages e3351382.

Abstract

Although hydrogen sulfide (H₂S) is a key regulator in cancer biology, the mechanism by which the H₂S-producing enzyme cystathionine-γ-lyase (CTH) functions in hepatocellular carcinoma (HCC) remains elusive. Using the slow-releasing H₂S donor GYY4137, we observed enhanced migration and invasion in HuH7 and HepG2 cells. Subsequently, we observed consistent protumorigenic effects of CTH not only in vitro but also in subcutaneous and orthotopic mouse models. Here, our findings suggest that CTH-H₂S sulfhydrates Rab7a, which may be associated with HCC progression. We further showed that CTH modulates the expression of autophagy-related proteins in liver tumor cells. In nude mouse subcutaneous xenograft experiments, compared with the vehicle group, the combination of DL-propargylglycine (PPG, CTH inhibitor) and GPC3 CAR-T exhibited better antitumor efficacy compared to PPG or CAR-T alone. Our findings suggest that CTH modulation was associated with altered Rab7a sulfhydration and autophagy and that combined PPG and GPC3 CAR-T therapy exerts better antitumor efficacy.

PMID:
42885431
Bibliographic data and abstract were imported from PubMed on 16 Oct 2026.

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