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Published on: September 11, 2012
Effect of angiostatin on 1,2-dimethylhydrazine-induced colon cancer in mice
Tolga Ertekin1, Nihat Ekinci, Omur Karaca
1Department of Anatomy, University of Erciyes, School of Medicine, Kayseri, Turkey. tol-kin@hotmail.com
Abstract:
Antiangiogenic therapy is supposed to be an attractive approach for antitumor treatment. Human plasminogen-derived angiostatin K1-3 is one of the most potent antiangiogenic agents known currently. However, it is unclear whether angiostatin has got protective effects on colon cancer. So we investigated the protective effects of angiostatin on 1,2-dimethylhydrazine (DMH)-induced colon cancer in mice. Thirty Balb/C male mice, weighing 25-30 g and 8 weeks of age, were used. Twenty of the mice were treated with DMH subcutaneously (20 mg/kg) once a week for 12 weeks. Six mice died during the DMH injection and surviving mice were divided into two groups (7 mice in DMH and 7 mice in DMH + angiostatin groups). In the angiostatin group, 6 weeks after the last DMH injection the animals were first treated with angiostatin (20 μg/mouse) intraperitoneally and then subcutaneously every 48 h (5 μg/mouse) throughout a period of 12 weeks. The animals were killed after 30 weeks for histopathological examination. When we look at the distribution of lesions in the colon, they mainly occurred in the distal colon. The incidence of mean colonic lesions in a tumor-bearing mouse was 9.85 ± 4.91 in those treated with DMH and 8.71 ± 3.49 in those treated with angiostatin. The incidence of colon tumors was not significantly affected by low dose of angiostatin, and we noticed that the number of lesions decreased by 12% in DMH + angiostatin group compared to the number of the lesions in DMH group, but this decrease was not statistically significant (p > 0.05). The administration period of angiostatin corresponds to the precancerous period and the reduction in the number of lesions could be important for the protective function of angiostatin in DMH + angiostain group. We assume that therapeutic effects of angiostatin are related to its doses, route of administration, frequency and administration period. In addition, we believe that combination of high doses of angiostatin with radiation, gene therapy or chemotherapy might be successful in proper tumor model.
Insights
This study explored angiostatin
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Antiangiogenic therapy is a promising strategy for cancer treatment.
- Human plasminogen-derived angiostatin K1-3 is a potent antiangiogenic agent.
- The protective effects of angiostatin on colon cancer remain unclear.
Purpose of the Study:
- To investigate the protective effects of angiostatin on 1,2-dimethylhydrazine (DMH)-induced colon cancer in mice.
- To assess the impact of angiostatin on lesion incidence and tumor formation in a mouse model.
Main Methods:
- Colon cancer was induced in mice using 1,2-dimethylhydrazine (DMH).
- Mice were treated with DMH and subsequently with angiostatin at specific doses and intervals.
- Histopathological examination was performed after 30 weeks to analyze colonic lesions.
Main Results:
- Angiostatin treatment did not significantly affect the incidence of colon tumors.
- A 12% decrease in the number of colonic lesions was observed in the DMH + angiostatin group compared to the DMH group, but this was not statistically significant.
- Lesions were predominantly found in the distal colon.
Conclusions:
- Low-dose angiostatin did not significantly protect against DMH-induced colon cancer in this study.
- The therapeutic efficacy of angiostatin may depend on dosage, administration route, frequency, and duration.
- Combination therapy with high-dose angiostatin and other treatments like radiation or chemotherapy may hold potential.
