title: Ginsenoside Rg3 inhibits HIF-1α and VEGF expression in patient with acute leukemia via inhibiting the activation of PI3K/Akt and ERK1/2 pathways.
abstract: Aberrant angiogenesis is essential to the development and progression of leukemia. Ginsenoside Rg3 has been commonly used in anti-angiogenic therapy of solid tumors. This study aimed to investigate the anti-angiogenic effects of Rg3 in patients with acute leukemia. Bone marrow stromal cells derived from patients with acute leukemia were treated with Rg3 and the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible factor 1α (HIF-1α) was detected by RT-PCR and western blot analysis. The results showed that Rg3 inhibited VEGF and HIF-1α expression at both mRNA and protein levels in bone marrow stromal cells. In addition, Rg3 treatment led to reduced serum levels of HIF-1α and VEGF in patients with acute leukemia. Mechanistically, we demonstrated that Rg3 downregulated the phosphorylation of Akt and ERK1/2 in BMSCs. In conclusion, Rg3 exhibits anti-leukemia effect in part due to its anti-angiogenic activity via inhibiting PI3K/Akt and ERK1/2 pathways, which act to regulate the expression of HIF-1α and VEGF.
authors: Department of Hematology, Xinqiao Hospital, Third Military Medical University Chongqing, 400037, China.
authors: Dongfeng
authors: D
authors: Zeng
authors: Department of Hematology, Xinqiao Hospital, Third Military Medical University Chongqing, 400037, China.
authors: Jinliang
authors: J
authors: Wang
authors: Department of Hematology, Xinqiao Hospital, Third Military Medical University Chongqing, 400037, China.
authors: Peiyan
authors: P
authors: Kong
authors: Department of Hematology, Xinqiao Hospital, Third Military Medical University Chongqing, 400037, China.
authors: Cheng
authors: C
authors: Chang
authors: Department of Hematology, Xinqiao Hospital, Third Military Medical University Chongqing, 400037, China.
authors: Jieping
authors: J
authors: Li
authors: Department of Hematology, Xinqiao Hospital, Third Military Medical University Chongqing, 400037, China.
authors: Jiali
authors: J
authors: Li
mesh_terms: D000328:Adult; D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D001854:Bone Marrow Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D002478:Cells, Cultured; D002681:China; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004789:Enzyme Activation; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D036145:Ginsenosides / Q000627:therapeutic use*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D020533:Angiogenesis Inhibitors; D036145:Ginsenosides; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C097367:ginsenoside Rg3; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
keywords: Acute leukemia; Rg3; angiogenesis; bone marrow stromal cells; hypoxia-inducible factor 1; vascular endothelial growth factor