CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题：Ganoderic acid T, a Ganoderma triterpenoid, modulates the tumor microenvironment and enhances the chemotherapy and immunotherapy efficacy through downregulating galectin-1 levels.
Ganoderic acid T, a Ganoderma triterpenoid, modulates the tumor microenvironment and enhances the chemotherapy and immunotherapy efficacy through downregulating galectin-1 levels.
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灵芝酸T（GAT）是灵芝中的一种三萜类分子，具有抗癌活性；然而，其潜在机制仍不清楚。因此，在本研究中，我们旨在探讨GAT的抗癌分子机制，并探索其在癌症治疗中的应用。在人源化小鼠模型的ES-2原位卵巢癌模型中，GAT表现出强效抗癌活性，导致肿瘤微环境（TME）发生显著改变。
具体而言，GAT降低了α-SMA +细胞的比例，并增强了肿瘤组织中TIL（肿瘤浸润淋巴细胞）（TILs）的浸润。进行蛋白质组学分析后，发现GAT下调galectin-1（Gal-1），这是TME中的关键分子。这种下调已在多种癌细胞系和异种移植瘤中得到证实。分子对接提示GAT与Gal-1之间可能存在理论上的直接相互作用。
进一步研究显示，GAT诱导Gal-1泛素化。此外，GAT显著增强了紫杉醇的抗癌效果，从而提高了瘤内药物浓度并缩小了肿瘤体积。与免疫治疗联合时，GAT增强了抗程序性死亡配体 1抗体的抑瘤效果，并提高了EMT6同系乳腺癌模型中CD8 +细胞的比例。
总之，GAT抑制肿瘤生长、下调Gal-1、调节TME，并促进化疗和免疫治疗疗效。我们的发现凸显了GAT作为一种有效癌症治疗药物的潜力。
Ganoderic acid T (GAT), a triterpenoid molecule of Ganoderma lucidum, exhibits anti-cancer activity; however, the underlying mechanisms remain unclear.
Therefore, in this study, we aimed to investigate the anti-cancer molecular mechanisms of GAT and explore its therapeutic applications for cancer treatment. GAT exhibited potent anti-cancer activity in an ES-2 orthotopic ovarian cancer model in a humanized mouse model, leading to significant alterations in the tumor microenvironment (TME).
Specifically, GAT reduced the proportion of α-SMA + cells and enhanced the infiltration of tumor-infiltrating lymphocytes (TILs) in tumor tissues. After conducting proteomic analysis, it was revealed that GAT downregulates galectin-1 (Gal-1), a key molecule in the TME. This downregulation has been confirmed in multiple cancer cell lines and xenograft tumors. Molecular docking suggested a theoretical direct interaction between GAT and Gal-1.
Further research revealed that GAT induces ubiquitination of Gal-1.
Moreover, GAT significantly augmented the anti-cancer effects of paclitaxel, thereby increasing intratumoral drug concentrations and reducing tumor size. Combined with immunotherapy, GAT enhanced the tumor-suppressive effects of the anti-programmed death-ligand 1 antibody and increased the proportion of CD8 + cells in the EMT6 syngeneic mammary cancer model.
In conclusion, GAT inhibited tumor growth, downregulated Gal-1, modulated the TME, and promoted chemotherapy and immunotherapy efficacy.
Our findings highlight the potential of GAT as an effective therapeutic agent for cancer.
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