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Updated: Jul 4, 2026
Tumor Transplantation for Assessing the Dynamics of Tumor-Infiltrating CD8+ T Cells in Mice
Published on: June 12, 2021
Gambogic acid induced tumor cell apoptosis by T lymphocyte activation in H22 transplanted mice
Hongyan Gu1, Qidong You, Wei Liu
1Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing, Jiangsu 210009, People's Republic of China.
Abstract:
Multiple lines of evidence have demonstrated that gambogic acid (GA) is an efficient apoptosis inducing agent. However, the mechanisms of GA induced apoptosis have been controversial, despite the tremendous effort made during recent years. Here we report a novel mechanism through which GA induces cell apoptosis. Instead of dealing with tumor cells directly, GA first activates inactive T lymphocytes, which in turn triggers cancer cell apoptosis. This is supported by the observation that GA inhibited tumor growth and extended the survival time of mice bearing H22 tumor. cDNA microarray analysis indicated that 22.92% of the 48 genes that were affected with GA treatment were immune related genes. RT-PCR assay revealed that GA up-regulated MHC-II and TCR transcriptions, implicating that GA activates T lymphocytes to induce tumor cell apoptosis in vivo. HE staining showed that T lymphocytes penetrated into tumor tissues after GA administration. Western blotting revealed that GA enhanced CD4+ and CD8+ expressions. Annexin-V/PI double-staining and DNA ladder assays confirmed that GA induced tumor cell apoptosis. In summary, this report demonstrated, for the first time, that GA mainly activates T lymphocytes to induce cancer cell apoptosis in H22 transplanted mice.
Insights
Gambogic acid (GA) activates T lymphocytes, which then induce cancer cell apoptosis, offering a novel therapeutic mechanism. This immune activation inhibited tumor growth and extended survival in mice.
Area of Science:
- Immunology
- Cancer Biology
- Pharmacology
Background:
- Gambogic acid (GA) is recognized as an effective apoptosis-inducing agent.
- The precise mechanisms underlying GA-induced apoptosis remain incompletely understood and debated.
- Previous research has focused on direct effects on tumor cells, with limited exploration of immune system involvement.
Purpose of the Study:
- To elucidate a novel mechanism of gambogic acid (GA)-induced apoptosis.
- To investigate the role of T lymphocytes in GA's anti-cancer effects.
- To determine if GA activates immune cells to trigger cancer cell death.
Main Methods:
- In vivo studies using H22 tumor-bearing mice treated with GA.
- cDNA microarray analysis to identify gene expression changes.
- RT-PCR, HE staining, Western blotting, and Annexin-V/PI staining to assess immune cell activation and apoptosis.
- DNA ladder assays to confirm apoptosis.
Main Results:
- GA treatment inhibited tumor growth and prolonged survival in mice.
- Microarray analysis revealed significant alterations in immune-related genes post-GA treatment.
- GA upregulated MHC-II and TCR transcription, indicating T lymphocyte activation.
- Increased infiltration of T lymphocytes into tumors and enhanced CD4+/CD8+ expression were observed.
- Confirmation of GA-induced tumor cell apoptosis via Annexin-V/PI staining and DNA ladder assays.
Conclusions:
- Gambogic acid primarily activates T lymphocytes, which subsequently induce cancer cell apoptosis.
- This immune-mediated mechanism represents a novel pathway for GA's anti-cancer activity.
- The findings suggest potential immunotherapeutic applications for GA in cancer treatment.
