[Effect and mechanism of apigenin on VEGF expression in human breast cancer cells].
OBJECTIVE
To study the effects and mechanism of apigenin on the expression of vascular endothelial growth factor (VEGF) in human breast cancer MDA-MB-231 cells.


METHODS
MDA-MB-231 cells were used as the study object. MTT assay was used to detect the effect of apigenin on the cell viability. ELISA was used to determine the protein level of VEGF. RT-PCR was used to detect VEGF at mRNA level. A double luciferase system was used to measure the transcription activity of VEGF. pCEP4-HIF-1alpha was transferred to explore the reversing effect of HIF-1alpha on the inhibitory effect of apigenin on the transcription activity of VEGF. Western blotting was used to detect the time-dependent and dose-dependent effect of apigenin on HIF-lalpha, p-AKT, p-ERK, and p53 expression at protein level.


RESULTS
Apigenin had no visible inhibitory effect on cell viability. Apigenin reduced the secretion of VEGF, mRNA levels of VEGF and transcription activity of VEGF. Furthermore, the inhibitory effect of apigenin on the transcription activity of VEGF could be reversed by transferring pCEP4-HIF-1alpha into the cells. Additionally, apigenin inhibited the expression of HIF-1alpha and p-AKT, induced the expression of p53, but had no effect on the expression of p-ERK1/2.


CONCLUSIONS
Apigenin can inhibit VEGF expression in breast cancer cells, and this effect may be achieved through decreasing the expression of HIF-1alpha.
Jin
Xue-ying
XY
Cancer Institute, No. 1 Hospital, China Medical University, Shenyang 110001, China.
Ren
Chang-shan
CS
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D042461:Vascular Endothelial Growth Factor A; D047310:Apigenin; D051057:Proto-Oncogene Proteins c-akt; D048052:Mitogen-Activated Protein Kinase 3