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片仔癀对 T 细胞介导的抗 B16-F10、MC38 和 Hep1-6 肿瘤模型抗肿瘤活性的免疫调节作用。

Immunomodulatory Function of Pien Tze Huang in T Cell-Mediated Anti-tumor Activity against B16-F10, MC38 and Hep1-6 Tumor Models.

机构信息

State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Science, Xiamen University, Xiamen, Fujian Province, 361102, China.

Fujian Pien Tze Huang Enterprise Key Laboratory of Natural Medicine Research and Development, Zhangzhou, Fujian Province, 363000, China.

出版信息

Chin J Integr Med. 2024 Apr;30(4):348-358. doi: 10.1007/s11655-023-3749-2. Epub 2024 Jan 12.

Abstract

OBJECTIVE

To investigate the anti-tumor effects of Pien Tze Huang (PZH) in mouse models of B16-F10 melanoma, MC38 colorectal cancer, Hep1-6 hepatocellular carcinoma and chemically induced hepatocellular carcinoma model.

METHODS

Various tumor models, including B16-F10, MC38 and Hep1-6 tumor hypodermic inoculation models, B16-F10 and Hep1-6 pulmonary metastasis models, Hep1-6 orthotopic implantation model, and chemically induced hepatocellular carcinoma model, were utilized to evaluate the anti-tumor function of PZH. Tumor growth was assessed by measuring tumor size and weight of solid tumors isolated from C57BL/6 mice. For cell proliferation and death of tumor cells in vitro, as well as T cell activation markers, cytokine production and immune checkpoints analysis, single-cell suspensions were prepared from mouse spleen, lymph nodes, and tumors after PZH treatment.

RESULTS

PZH demonstrated significant therapeutic efficacy in inhibiting tumor growth (P<0.01). Treatment with PZH resulted in a reduction in tumor size in subcutaneous MC38 colon adenocarcinoma and B16-F10 melanoma models, and decreased pulmonary metastasis of B16-F10 melanoma and Hep1-6 hepatoma (P<0.01). However, in vitro experiments showed that PZH only had slight impact on the cell proliferation and survival of tumor cells (P>0.05). Nevertheless, PZH exhibited a remarkable ability to enhance T cell activation and the production of interferon gamma, tumor necrosis factor alpha, and interleukin 2 in CD4 T cells in vitro (P<0.01 or P<0.05). Importantly, PZH substantially inhibited T cell exhaustion and boosted cytokine production by tumor-infiltrating CD8 T cells (P<0.01 or P<0.05).

CONCLUSION

This study has confirmed a novel immunomodulatory function of PZH in T cell-mediated anti-tumor immunity, indicating that PZH holds promise as a potential therapeutic agent for cancer treatment.

摘要

目的

研究片仔癀(PZH)在 B16-F10 黑色素瘤、MC38 结直肠癌、Hep1-6 肝癌以及化学诱导肝癌模型小鼠中的抗肿瘤作用。

方法

利用 B16-F10 皮下接种肿瘤模型、B16-F10 和 Hep1-6 肺转移模型、Hep1-6 原位种植模型和化学诱导肝癌模型等多种肿瘤模型,评估 PZH 的抗肿瘤功能。通过测量 C57BL/6 小鼠分离的实体瘤的肿瘤大小和重量来评估肿瘤生长情况。对于体外肿瘤细胞增殖和死亡、T 细胞激活标志物、细胞因子产生和免疫检查点分析,在 PZH 处理后从小鼠脾脏、淋巴结和肿瘤中制备单细胞悬液。

结果

PZH 对抑制肿瘤生长具有显著的治疗效果(P<0.01)。PZH 治疗导致皮下 MC38 结肠腺癌和 B16-F10 黑色素瘤模型中的肿瘤体积减小,并减少了 B16-F10 黑色素瘤和 Hep1-6 肝癌的肺转移(P<0.01)。然而,体外实验表明 PZH 仅对肿瘤细胞的增殖和存活有轻微影响(P>0.05)。然而,PZH 表现出显著增强 CD4 T 细胞中 T 细胞激活和干扰素γ、肿瘤坏死因子α和白细胞介素 2 产生的能力(P<0.01 或 P<0.05)。重要的是,PZH 显著抑制了 T 细胞衰竭,并增强了肿瘤浸润性 CD8 T 细胞的细胞因子产生(P<0.01 或 P<0.05)。

结论

本研究证实了 PZH 在 T 细胞介导的抗肿瘤免疫中的新的免疫调节功能,表明 PZH 有望成为癌症治疗的潜在治疗药物。

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