Triptolide represses oral cancer cell proliferation, invasion, migration, and angiogenesis in co-inoculation with
Cheng-Yu Yang1, Chih-Kung Lin2, Gu-Jiun Lin3
1Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
Objectives:
Advanced oral cancer is a major public health concern because of a lack of effective prevention and treatment. Triptolide (TPL), a diterpenoid triepoxide derived from the Chinese herb Tripterygium wilfordii, has been demonstrated to possess strong anticancer properties. In this study, we investigated whether TPL exerts anticancer effects on the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC).
Materials And Methods:
Human macrophage-like U937 cells were co-inoculated with oral cancer SAS cells in a noncontact transwell coculture system. Cytokine expression was detected using ELISA, and cell proliferation was detected using methylene blue. RNA levels were detected using qPCR. Protein levels were detected using Western blot analysis. In vivo experiments involved using xenografted NOD/SCID mice.
Results:
Our results demonstrated that TPL inhibited the growth of SAS cells co-inoculated with U937 cells in vitro and in vivo. TPL inhibited the invasion, migration ability, and angiogenesis of SAS cells co-inoculated with U937 cells. Expression of cytokines IL-6, IL-8, and TNF-α was induced by co-inoculation, but TPL repressed their expression.
Conclusion:
TPL suppressed the expression of cytokines IL-6, IL-8, and TNF-α, as well as tumor growth, invasion, migration, and angiogenesis in the co-inoculation of human tongue cancer cells with macrophage-like U937 cells.
Clinical Relevance:
TPL is a potential candidate among novel chemotherapeutic agents or adjuvants for modulating tumor-associated macrophages in a tumor microenvironment of HNSCC.
Insights
Triptolide (TPL) effectively inhibited head and neck squamous cell carcinoma (HNSCC) growth and spread by suppressing inflammatory cytokines. This natural compound shows promise for treating oral cancer by targeting the tumor microenvironment.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Advanced oral cancer, specifically head and neck squamous cell carcinoma (HNSCC), presents a significant public health challenge due to limited therapeutic options.
- Triptolide (TPL), a compound from Tripterygium wilfordii, exhibits potent anticancer activities.
- The tumor microenvironment, including macrophages, plays a critical role in HNSCC progression.
Purpose of the Study:
- To investigate the anticancer effects of Triptolide (TPL) on the tumor microenvironment of head and neck squamous cell carcinoma (HNSCC).
- To evaluate TPL's impact on cancer cell growth, invasion, migration, and angiogenesis in a co-culture system with macrophages.
Main Methods:
- Co-inoculation of human macrophage-like U937 cells with oral cancer SAS cells in a transwell system.
- Quantification of cytokine expression (IL-6, IL-8, TNF-α) using ELISA.
- Assessment of cell proliferation, invasion, migration, and angiogenesis in vitro.
- In vivo efficacy evaluation using xenografted NOD/SCID mice.
Main Results:
- TPL significantly inhibited the growth of HNSCC cells (SAS) when co-inoculated with U937 cells, both in vitro and in vivo.
- TPL suppressed the invasion, migration, and angiogenesis of HNSCC cells.
- Co-inoculation induced expression of IL-6, IL-8, and TNF-α, which were repressed by TPL treatment.
Conclusions:
- Triptolide (TPL) demonstrates significant anticancer effects against HNSCC by suppressing tumor growth, invasion, migration, and angiogenesis.
- TPL effectively modulates the tumor microenvironment by repressing key inflammatory cytokines (IL-6, IL-8, TNF-α).
- TPL is a promising therapeutic candidate for HNSCC, potentially as a chemotherapeutic agent or adjuvant for targeting tumor-associated macrophages.
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