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

  • Yu-bing Fu,
  • Chen-feng Liu,
  • Jin-jia Wang,
  • Xiao-lin Ji,
  • Rong-han Tang,
  • Kun-yu Liao,
  • Ling-yue Chen,
  • Ya-zhen Hong,
  • Bin-bin Fan,
  • Shi-cong Wang,
  • Wen-Hsien Liu

摘要

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.