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Enhanced antitumour efficacy by combining conventional chemotherapy with angiostatin or endostatin in a liver
E A te Velde1, J M Vogten, M F G B Gebbink
1Department of Surgery and Laboratory of Medical Oncology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Background:
Tumour-induced microvascular networks have become attractive targets in cancer therapy. Strategies that target both tumour cells and vasculature have not been investigated in models of early metastatic colorectal disease. The efficacy of a combination of conventional chemotherapy with a potent angiogenesis inhibitor (endostatin or angiostatin) in a murine model of early colorectal liver metastasis was studied.
Methods:
Sixty-six mice were subjected to intrasplenic injection of C26 tumour cells to induce colorectal liver metastases. Control animals received phosphate-buffered saline (n = 8) or citrate buffer (n = 8). Treatment included conventional chemotherapy (n = 9), endostatin (n = 8), high-dose (n = 5) or low-dose (one-tenth of optimal dose; n = 10) angiostatin, as well as the combination of either of these drugs with chemotherapy (n > 5). Clinical appearance was scored daily using a semiquantitative scale. Liver weight, macroscopic and histological tumour involvement (hepatic replacement area; HRA) were measured upon death at day 12.
Results:
Treated mice displayed significantly better clinical scores than controls, except for those animals treated with low-dose angiostatin with or without chemotherapy. Treatment with conventional chemotherapy resulted in a decrease in HRA from 42.3 to 29.1 per cent (P < 0.001). The addition of angiostatin or endostatin to conventional chemotherapy improved antitumoral efficacy, in a multiplicative manner, resulting in a HRA of approximately 3.5 per cent (P < 0.001).
Conclusion:
The addition of angiostatin or endostatin to conventional chemotherapy enhanced antitumoral efficacy in a murine model of early colorectal liver metastasis.
Insights
Combining chemotherapy with angiogenesis inhibitors like endostatin or angiostatin significantly improved colorectal liver metastasis treatment in mice. This combination therapy demonstrated enhanced antitumoral efficacy compared to chemotherapy alone.
Area of Science:
- Oncology
- Cancer Biology
- Translational Medicine
Background:
- Tumour-induced microvascular networks are key targets in cancer therapy.
- Strategies combining anti-tumour cell and anti-vasculature approaches are underexplored in early metastatic colorectal disease.
- This study investigates combination therapy for colorectal liver metastasis.
Purpose of the Study:
- To evaluate the efficacy of combining conventional chemotherapy with angiogenesis inhibitors (endostatin or angiostatin).
- To assess this combination therapy in a murine model of early colorectal liver metastasis.
Main Methods:
- Sixty-six mice with induced colorectal liver metastases were treated with chemotherapy, endostatin, angiostatin (high or low dose), or combinations.
- Control groups received saline or buffer.
- Tumour burden was assessed via hepatic replacement area (HRA) at day 12.
Main Results:
- Conventional chemotherapy reduced HRA from 42.3% to 29.1%.
- Combining chemotherapy with endostatin or angiostatin resulted in a significant multiplicative decrease in HRA to approximately 3.5%.
- Low-dose angiostatin, with or without chemotherapy, did not improve outcomes.
Conclusions:
- The addition of endostatin or angiostatin to conventional chemotherapy substantially enhanced antitumoral efficacy.
- Combination therapy holds promise for treating early colorectal liver metastasis.
