Inhibition Effect of Luteolin on the Proliferation and Migration of the Endothelial Cells Co-Cultured with Cancer Cells and Its Molecular Mechanism
PING Yao-dong1, LIANG Tai-gang2, ZHANG Yan-hua1*
1. Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Pharmacy of Department, Peking University Cancer Hospital & Institute, Beijing 100142, China; 2. College of Pharmacy, Shanxi Medical University, Taiyuan 030001, China
Abstract��OBJECTIVE To explore the effects of luteolin on the proliferation and migration of the endothelial cells co-cultured with cancer cells and its molecular mechanism. METHODS Human umbilical vein endothelial cells (HUVECs) were primarily isolated and identified by the expression of VE-cadherin. Cancer-endothelial cell co-culture model was established using the Transwell system. The effects of luteolin at different concentrations (0 [Co-culture control], 20 and 50 ��mol��L-1) on the proliferation and migration of HUVECs in the co-culture system were determined. A HUVECs control group removed of prostate cancer PC3 cells was also included. Human angiogenesis antibody array kit was used to assay the secretion levels of various protein factors in each group. RESULTS VE-cadherin was expressed on all the cultured HUVECs. Increased proliferation ability was found in the HUVECs co-cultured with PC3 cells compared with that in HUVECs control group (P<0.01). Treatment with 20 or 50 ��mol��L-1 luteolin significantly inhibited the proliferation ability of the HUVECs in co-culture system (both P<0.01). Increased migration ability was found in the HUVECs co-cultured with PC3 cells compared with that in HUVECs control group (P<0.01). Treatment with 20 or 50 ��mol��L-1 luteolin significantly inhibited the migration ability of the HUVECs in co-culture system (both P<0.01). Secretion levels of multiple angiogenesis-related proteins in the cultural supernatant of co-culture system were significantly increased compared with those in HUVECs control group. Treatment with 20 ��mol��L-1 luteolin significantly inhibited the secretion levels of interleukin-8 (IL-8), vascular endothelial growth factor (VEGF) and monocyte chemoattractant protein-1(MCP-1) in the cultural supernatant of co-culture system (all P<0.01). CONCLUSION Luteolin may inhibit the proliferation and migration of endothelial cells via suppressing the secretions of IL-8, VEGF and MCP-1 in cancer-endothelial co-culture system.
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PING Yao-dong, LIANG Tai-gang, ZHANG Yan-hua. Inhibition Effect of Luteolin on the Proliferation and Migration of the Endothelial Cells Co-Cultured with Cancer Cells and Its Molecular Mechanism. Chinese Pharmaceutical Journal, 2018, 53(7): 508-512.
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