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已发表论文
牛磺酸修饰棉酚通过抑制 PI3K/AKT 通路及靶向调节性 T 细胞中 FASN 介导的脂质代谢发挥双重抗肝细胞癌作用
Authors He W , Shi J, Deng G , Liu W, Kou L, Hu J, Lin Y, Lin X, Sheng J , Wu F
Received 5 October 2025
Accepted for publication 10 December 2025
Published 15 December 2025 Volume 2025:12 Pages 2755—2770
DOI https://doi.org/10.2147/JHC.S572305
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Imam Waked
Weishan He,1,* Juzheng Shi,1,* Guangmei Deng,1 Wenya Liu,1 Long Kou,1 Jia Hu,1 Yajing Lin,1 Xinlan Lin,1 Jinzhou Sheng,1 Fasheng Wu2
1Ruikang Clinical Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 2Radiation Oncology Department, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Fasheng Wu, Email 840766676@qq.com
Background: Hepatocellular carcinoma (HCC) remains a highly challenging malignancy to treat with a dismal prognosis. The immunosuppressive tumor microenvironment (TIME), particularly regulatory T cells (Tregs), is a key driver of treatment resistance. This study aimed to investigate the anti-tumor efficacy and underlying mechanism of taurine-modified gossypol (GT)—a novel conjugate derived from two natural products (taurine and gossypol) with potential synergistic activity.
Methods: The anti-proliferative (CCK-8 assay), pro-apoptotic (Annexin V/PI staining) and cell cycle-regulatory (PI staining) effects of GT were evaluated in HepG2 cells and patient-derived HCC organoids. scRNA-seq and multiparametric flow cytometry were used to analyze alterations in the TIME. Molecular docking and surface plasmon resonance (SPR) were performed to validate the binding affinity (KD) between GT and FASN. Western blotting assessed PI3K/AKT and lipid metabolism pathways.
Results: GT dose-dependently inhibited HCC proliferation, induced apoptosis and caused G1 arrest, with concomitant PI3K/AKT pathway suppression. scRNA-seq revealed a selective reduction in Treg proportion following GT treatment. Mechanistically, GT bound to FASN with high affinity, inhibiting its activity and disrupting lipid metabolism in Tregs, thereby reprogramming Treg differentiation and function. In HCC patients, a clinically significant link was observed between high levels of FASN expression and reduced survival, based on an analysis of TCGA data.
Conclusion: GT exerts synergistic anti-HCC effects through a dual mechanism: directly suppressing tumor proliferation by inactivating the PI3K/AKT pathway, and remodeling the TIME by targeting FASN-dependent lipid metabolism in Tregs. These findings highlight the potential of GT as a novel multitargeted agent for HCC treatment.
Keywords: taurine-modified gossypol, hepatocellular carcinoma, regulatory T cells, fatty acid synthase, PI3K/AKT pathway
1Ruikang Clinical Medical College, Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China; 2Radiation Oncology Department, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning, Guangxi, People’s Republic of China
*These authors contributed equally to this work
Correspondence: Fasheng Wu, Email 840766676@qq.com
Background: Hepatocellular carcinoma (HCC) remains a highly challenging malignancy to treat with a dismal prognosis. The immunosuppressive tumor microenvironment (TIME), particularly regulatory T cells (Tregs), is a key driver of treatment resistance. This study aimed to investigate the anti-tumor efficacy and underlying mechanism of taurine-modified gossypol (GT)—a novel conjugate derived from two natural products (taurine and gossypol) with potential synergistic activity.
Methods: The anti-proliferative (CCK-8 assay), pro-apoptotic (Annexin V/PI staining) and cell cycle-regulatory (PI staining) effects of GT were evaluated in HepG2 cells and patient-derived HCC organoids. scRNA-seq and multiparametric flow cytometry were used to analyze alterations in the TIME. Molecular docking and surface plasmon resonance (SPR) were performed to validate the binding affinity (KD) between GT and FASN. Western blotting assessed PI3K/AKT and lipid metabolism pathways.
Results: GT dose-dependently inhibited HCC proliferation, induced apoptosis and caused G1 arrest, with concomitant PI3K/AKT pathway suppression. scRNA-seq revealed a selective reduction in Treg proportion following GT treatment. Mechanistically, GT bound to FASN with high affinity, inhibiting its activity and disrupting lipid metabolism in Tregs, thereby reprogramming Treg differentiation and function. In HCC patients, a clinically significant link was observed between high levels of FASN expression and reduced survival, based on an analysis of TCGA data.
Conclusion: GT exerts synergistic anti-HCC effects through a dual mechanism: directly suppressing tumor proliferation by inactivating the PI3K/AKT pathway, and remodeling the TIME by targeting FASN-dependent lipid metabolism in Tregs. These findings highlight the potential of GT as a novel multitargeted agent for HCC treatment.
Keywords: taurine-modified gossypol, hepatocellular carcinoma, regulatory T cells, fatty acid synthase, PI3K/AKT pathway