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Gamma-secretase inhibitor does not modulate angiogenesis in colon adenocarcinoma in obese mice
Background:
Notch is a signaling molecule which plays a role in angiogenesis and γ-secretase is required for processing of Notch. In this study, we investigated the effect of γ-secretase inhibitor (DAPT) on tumor angiogenesis in diet-induced obese mice.
Methods:
18 mice were divided into three groups; control, obese (diet-induced) and obese+DAPT. After 15 weeks, the obese mice were subjected for tumor induction of CT26 colon adenocarcinoma cells (5 x 105 cells). When the tumor size reached approximately 350 ± 50 mm3, half of the obese animals received DAPT (10mg/kg/day) subcutaneously. Blood samples were taken after 14 days and the tumors harvested for immunohistochemical staining and capillary density were reported as CD31 positive cells/mm2.
Results:
The obese animals had higher serum leptin and NO concentrations, while, serum VEGF and VEGFR-1 concentrations were not different compare to control group. Administration of DAPT in obese mice significantly reduced serum VEGFR-1 and leptin concentrations and increased serum NO level (p < 0.05). Capillary density in the tumors of obese animals was not different compare to control groups. DAPT administration could not alter capillary density in the tumors.
Conclusion:
Administration of DAPT in obese mice altered serum angiogenic factors, however, it could not modulate tumor angiogenesis in diet-induced obese mice (Fig. 4, Ref. 26).
Insights
This study investigated the effect of γ-secretase inhibitor (DAPT) on tumor angiogenesis in diet-induced obese mice. DAPT altered serum angiogenic factors but did not modulate tumor angiogenesis.
Area of Science:
- Oncology
- Metabolic Diseases
- Molecular Biology
Background:
- Notch signaling is crucial for angiogenesis.
- γ-secretase is essential for Notch processing.
- Obesity can influence tumor microenvironment and angiogenesis.
Purpose of the Study:
- To investigate the effect of γ-secretase inhibitor (DAPT) on tumor angiogenesis in diet-induced obese mice.
- To analyze the impact of DAPT on serum angiogenic factors and tumor capillary density.
Main Methods:
- Diet-induced obesity model in mice.
- Tumor induction using CT26 colon adenocarcinoma cells.
- Administration of DAPT and subsequent analysis of serum markers and tumor immunohistochemistry.
Main Results:
- Obese mice showed elevated leptin and NO, but similar VEGF and VEGFR-1 compared to controls.
- DAPT treatment in obese mice reduced serum VEGFR-1 and leptin, and increased NO.
- Tumor capillary density was not significantly altered by DAPT in obese mice.
Conclusions:
- DAPT modifies serum angiogenic factors in obese mice.
- DAPT does not modulate tumor angiogenesis in this diet-induced obesity model.
- Further research is needed to understand the complex interplay between obesity, Notch signaling, and tumor angiogenesis.
