Curcumin Suppresses Tumor Growth and Angiogenesis in Human Glioma Cells Through Modulation of Vascular Endothelial Growth Factor/ Angiopoietin-2/Thrombospondin-1 Signaling.
OBJECTIVE
To investigate the effect of curcumin on tumor growth and angiogenesis of human gliomas and identify the underlying molecular mechanisms.


METHODS
A mouse xenograft glioma model was established by subcutaneously inoculating tumor cell aggregates derived from the U87 cell line. Mice were treated with 0.01ml/g body weight of curcumin or saline. Tumor volume was measured. Microvessel density was assessed by CD34 immunostaining, and angiogenesis by immunohistochemical staining of vascular endothelial growth factor (VEGF), angiopoietin-2 (Ang-2) and thrombospondin 1 (TSP-1).


RESULTS
At 28 days after treatment, tumor weights in the curcumin-treated group were much smaller than in the control group (0.23±0.11g vs 0.44±0.15g，p＜0.05), resulting in a 45.8% inhibition of tumor growth. Curcumin also markedly inhibited microvessel density. Expression of VEGF and Ang-2 was inhibited by curcumin, whereas TSP-1 expression was up-regulated.


CONCLUSIONS
This study shows that curcumin inhibits tumor growth by inhibiting VEGF/Ang-2/TSP-1- mediated angiogenesis in a xenograft glioma mouse model.
Director of Research, CNS Injury & Repair (IECNSIR), Uppsala University Hospital, Uppsala University, Frödingsgatan 12, Bldg. 1228, SE-7541 Uppsala. Sweden.
Zhiqiang
Z
Zhang
Department of Neurosurgery, Chinese Medicine Hospital of Guangdong Province, The Second Affiliated Hospital, University of Chinese Medicine in Guangzhou, Guangzhou. China.
Cong
C
Li
Department of Neurosurgery, Chinese Medicine Hospital of Guangdong Province, The Second Affiliated Hospital, University of Chinese Medicine in Guangzhou, Guangzhou. China.
Qijia
Q
Tan
Department of Neurosurgery, Chinese Medicine Hospital of Guangdong Province, The Second Affiliated Hospital, University of Chinese Medicine in Guangzhou, Guangzhou. China.
Caijun
C
Xie
Department of Neurosurgery, Chinese Medicine Hospital of Guangdong Province, The Second Affiliated Hospital, University of Chinese Medicine in Guangzhou, Guangzhou. China.
Yanying
Y
Yang
Department of Neurosurgery, Chinese Medicine Hospital of Guangdong Province, The Second Affiliated Hospital, University of Chinese Medicine in Guangzhou, Guangzhou. China.
Wengang
W
Zhan
Department of Neurosurgery, Chinese Medicine Hospital of Guangdong Province, The Second Affiliated Hospital, University of Chinese Medicine in Guangzhou, Guangzhou. China.
Fu
F
Han
Director of Research, CNS Injury & Repair (IECNSIR), Uppsala University Hospital, Uppsala University, Frödingsgatan 12, Bldg. 1228, SE-7541 Uppsala. Sweden.
Hari Shanker
HS
Sharma
International Experimental Central Nervous System Injury & Repair (IECNSIR), Laboratory of Cerebrovascular Research, Department of Surgical Sciences Anesthesiology and Intensive Care Medicine, University Hospital, Uppsala University, SE-75421 Uppsala. Sweden.
Aruna
A
Sharma
D042702:Angiopoietin-2 / Q000378:metabolism*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology / Q000627:therapeutic use; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects*; D019700:Thrombospondin 1 / Q000378:metabolism; D013997:Time Factors; D014183:Transplantation, Heterologous; D042442:Vascular Endothelial Growth Factors / Q000378:metabolism*
D042702:Angiopoietin-2; D018952:Antigens, CD34; D000970:Antineoplastic Agents; D019700:Thrombospondin 1; D042442:Vascular Endothelial Growth Factors; D003474:Curcumin
Curcumin; angiogenesis; glioma; vascular endothelial growth factor; vascular endothelial growth factor.Curcumin