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Failure of thalidomide to inhibit tumor growth and angiogenesis in vivo
1Department of Surgery, Tel Aviv Sourasky Medical Center, Tel Aviv University, Israel.
Abstract:
Thalidomide was recently suggested to be angiogenesis-inhibitor following the demonstration of its activity in a rabbit cornea micropocket model. The purpose of the present study was to test its efficacy in solid tumors in mice. B16-F10 melanoma and CT-26 colon carcinoma cells were injected subcutaneously, intravenously and intraperitoneally, and mice received daily gavage of 0.3-1.0 mg thalidomide starting either two or 10 days following tumor cell injection. The tumors were measured and compared with controls. There was no growth retardation in CT-26 bearing mice nor in mice with pulmonary or peritoneal metastases of B16-F10 melanoma. In 3/7 groups of mice with SC B16-F10 tumors, growth retardation was demonstrated, however the difference was not statistically significant. All tumors eventually reached maximal size, similar to controls. Morphological evaluation of the blood vessels oriented towards the tumor revealed that in both thalidomide and control groups, all mice had developed an intact network of new blood vessels. In our model for the oral administration of thalidomide inhibition of tumor growth and angiogenesis did not occur. We hypothesize that the lack of sustained antiangiogenic response was either due to immune modulation or to tumor heterogeneity and adaptation.
Insights
Thalidomide did not inhibit tumor growth or angiogenesis in mouse models, despite previous suggestions. Researchers hypothesize immune modulation or tumor adaptation may explain the lack of anti-angiogenic effect.
Area of Science:
- Oncology
- Pharmacology
Background:
- Thalidomide previously demonstrated anti-angiogenic properties in a rabbit cornea model.
- Its efficacy in solid tumors requires further investigation.
Purpose of the Study:
- To evaluate thalidomide's efficacy as an angiogenesis inhibitor in solid tumors in mice.
- To assess its impact on tumor growth and vascularization.
Main Methods:
- B16-F10 melanoma and CT-26 colon carcinoma cells were implanted in mice.
- Mice received daily oral thalidomide at varying doses and treatment start times.
- Tumor growth and vascular morphology were monitored.
Main Results:
- Thalidomide did not significantly inhibit CT-26 colon carcinoma growth or B16-F10 metastases.
- Limited, non-significant growth retardation was observed in some B16-F10 solid tumors.
- No significant difference in tumor vascularization was observed between thalidomide and control groups.
Conclusions:
- Oral thalidomide did not demonstrate significant anti-tumor or anti-angiogenic effects in this mouse model.
- Potential reasons for the lack of efficacy include immune modulation or tumor adaptation.
- Further research is needed to understand thalidomide's complex mechanisms in cancer treatment.