[Effects of endostatin and doxycycline on microcirculation patterns in melanoma and their relevant molecular mechanisms].
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.


CONCLUSIONS
The combined use of doxycycline and endostatin in melanoma can inhibit the expression of MMPs, influencing the formation of different microcirculation patterns in melanoma.
Sun
Bao-cun
BC
Department of Pathology, Tumor Hospital, Tianjin Medical University, China. baocunsun@eyou.com
Zhang
Shi-wu
SW
Qi
Li-sha
LS
Zhang
Dann-fang
DF
Guo
Hua
H
Zhao
Xiu-lan
XL
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D004318:Doxycycline / Q000494:pharmacology*; D004338:Drug Combinations; D004357:Drug Synergism; D043169:Endostatins / Q000494:pharmacology*; D005260:Female; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008833:Microcirculation / Q000187:drug effects*; D055806:Microvessels / Q000473:pathology; D009368:Neoplasm Transplantation; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D047368:Tumor Burden / Q000187:drug effects
D000970:Antineoplastic Agents; D004338:Drug Combinations; D043169:Endostatins; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D004318:Doxycycline