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Updated: Jul 9, 2026

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Published on: April 30, 2021
[Effects of endostatin and doxycycline on microcirculation patterns in melanoma and their relevant molecular
Bao-cun Sun1, Shi-wu Zhang, Li-sha Qi
1Department of Pathology, Tumor Hospital, Tianjin Medical University, China. baocunsun@eyou.com
Objective:
To investigate the effects of endostatin and doxycycline on microcirculation patterns in melanoma and their molecular mechanisms.
Methods:
To establish mouse B16 melanoma model by subcutaneous injection of B16 melanoma cell suspension. The mice were divided into 3 experimental groups and 1 control group. To treat the mice in the 3 experimental groups with endostatin, doxycycline, endostatin and doxycycline, respectively, and the control group without any treatment. The tumor volume was measured and recorded to make comparison of their growth rate. To assess the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemical staining. The three microcirculation patterns of endothelium-dependent vessels, mosaic vessels and vasculogenic mimicry were counted. The activity of MMP-2, MMP-9 between different groups was examined by gelatin zymography.
Results:
Tumor growth in the three experimental groups was statistically significantly slower than that in the control group. The expression of MMP-2, MMP-9 and TIMP-2 in each treated group was significantly different with that in the control group. The amount of three microcirculation patterns in three experimental groups was less than that of the control group, and the amount of MV and VM in each experimental group was significantly less than that in the control group. By gelatin zymography, the enzyme activity of MMP-9, actived-MMP-2 and MMP-2/proMMP-2 in ES, DOX and ES + DOX group was lower than that in the control group, but the enzyme activity of pro-MMP-2 among the four groups was not significantly different.
Conclusion:
The combined use of doxycycline and endostatin in melanoma can inhibit the expression of MMPs, influencing the formation of different microcirculation patterns in melanoma.
Insights
Endostatin and doxycycline combination therapy significantly inhibits melanoma growth by reducing matrix metalloproteinase (MMP) expression and altering microcirculation patterns, including mosaic vessels and vasculogenic mimicry.
Area of Science:
- Oncology
- Vascular Biology
- Pharmacology
Background:
- Melanoma exhibits complex microcirculation patterns crucial for tumor growth.
- Matrix metalloproteinases (MMPs) play a significant role in melanoma progression and angiogenesis.
Purpose of the Study:
- To investigate the therapeutic effects of endostatin and doxycycline on melanoma microcirculation.
- To elucidate the molecular mechanisms underlying these effects, focusing on MMP expression and activity.
Main Methods:
- A mouse B16 melanoma model was established.
- Mice were treated with endostatin, doxycycline, or a combination.
- Tumor growth, microcirculation patterns (endothelium-dependent vessels, mosaic vessels, vasculogenic mimicry), MMP/TIMP expression, and MMP activity were assessed.
Main Results:
- Combined endostatin and doxycycline significantly reduced tumor growth compared to controls.
- Treatment decreased the expression and activity of MMP-2 and MMP-9.
- Formation of mosaic vessels and vasculogenic mimicry was significantly reduced in treated groups.
Conclusions:
- Combined endostatin and doxycycline therapy effectively inhibits melanoma growth.
- The mechanism involves the downregulation of MMPs, impacting melanoma microcirculation and angiogenesis.
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