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[Relationship between TNFalpha and tumor rejection induced by a single dose of melphalan in C57BL/6 mice]
Mo-Lin Li1, Chuan-Gang Li, Xiao-Hong Shu
1Department of Pathophysiology, Dalian Medical University, Dalian 116027, China.
Aim:
To investigate the relationship between TNFalpha and tumor rejection induced by a single dose of melphalan in C57BL/6 mice.
Methods:
Different gene type mice (TNFR1(+/+), TNFR1(+/-) and TNFR1(-/-)) with the same genetic background of C57BL/6 were used in this experiment. Murine lymphoma EL4 cells were inoculated subcutaneously into the different gene type mice simultaneously. Twelve days later, 7.5 mg/kg melphalan was used intraperitoneally to treat the tumor-bearing mice with TNFR1(+/+), TNFR1(+/-) and TNFR1(-/-). The tumors in the different gene type mice were observed and recorded every one to three day.
Results:
After the treatment of 7.5 mg/kg melphalan during the first week, the tumors in the different gene type mice shrank at a similar rate. In the following 2 months, the tumors in the TNFR1(+/+) and TNFR1(+/-) C57BL/6 mice gradually shrank and were cured but most tumors in the TNFR1(-/-) C57BL/6 mice relapsed after melphalan treatment.
Conclusion:
TNFalpha plays an important role in melphalan-induced tumor rejection. The anti-tumor effect of melphalan has no relationship with the expression of tumor necrosis factor 1 in tumor-bearing mice. TNFR1 is required to prevent or avoid the relapse of tumors in mice instead of tumor cells.
Insights
Tumor necrosis factor-alpha (TNFalpha) is crucial for melphalan-induced tumor rejection in mice. Tumor necrosis factor receptor 1 (TNFR1) prevents tumor relapse, independent of melphalan
Area of Science:
- Immunology
- Oncology
- Pharmacology
Context:
- Melphalan is a chemotherapeutic agent used in cancer treatment.
- Tumor necrosis factor-alpha (TNFalpha) is a cytokine involved in inflammation and immunity.
- Tumor necrosis factor receptor 1 (TNFR1) mediates cellular responses to TNFalpha.
Purpose:
- To investigate the role of TNFalpha in melphalan-induced tumor rejection.
- To determine the involvement of TNFR1 in the anti-tumor effects of melphalan.
Summary:
- C57BL/6 mice with varying TNFR1 expression (TNFR1(+/+), TNFR1(+/-), and TNFR1(-/-)) were treated with melphalan after tumor inoculation.
- While melphalan initially reduced tumor size in all groups, TNFR1(-/-) mice experienced tumor relapse, unlike TNFR1(+/+) and TNFR1(+/-) mice.
- TNFalpha significantly contributes to tumor rejection following melphalan treatment, with TNFR1 being essential for preventing tumor relapse.
Impact:
- Highlights the critical role of TNFalpha in mediating the anti-tumor efficacy of melphalan.
- Identifies TNFR1 as a key factor in preventing post-treatment tumor recurrence.
- Provides insights into the mechanisms underlying melphalan's effectiveness and potential strategies to overcome resistance.
