title: Genetic inhibition of vascular endothelial growth factor receptor-1 significantly inhibits the migration and proliferation of leukemia cells and increases their sensitivity to chemotherapy.
abstract: Little is known about the role of vascular endothelial growth factor (VEGF) receptor-1 (VEGFR-1) in acute leukemia. In this study, using real-time PCR and ELISA, we found that VEGF and VEGFR-1 are highly expressed in U937 leukemia cells and primary leukemia cells (M4/M5 subtypes), which are associated with an increased migration rate and extramedullary disease. In order to elucidate the role of VEGFR-1 in acute leukemia, we used a lentivirus-mediated shRNA expression system to specifically inhibit VEGFR-1 expression in the U937 cell line. In addition, a series of in vitro experiments were conducted, including cell proliferation and migration assays and drug treatments. Our results showed that shRNA reduced the proliferation and migration of U937 cells. RNA interference targeting VEGFR-1 in combination with bevacizumab did not exert synergistic antitumor effects. However, shRNA enhanced the sensitivity of the U937 cells to cytarabine by decreasing the IC50 of cytarabine, reducing the number of cells in the S phase and suppressing the expression of the survivin gene. Taken together, these results suggest that VEGFR-1 interference may serve as a novel antitumor therapeutic strategy for the treatment of leukemia.
authors.affiliation: Department of Hematology, Tongji Hospital of Tongji University, Putuo, Shanghai 200065, PR China.
authors.forename: Bing
authors.initials: B
authors.lastname: Xiu
authors.forename: Wenjun
authors.initials: W
authors.lastname: Zhang
authors.forename: Binbin
authors.initials: B
authors.lastname: Huang
authors.forename: Jingde
authors.initials: J
authors.lastname: Chen
authors.forename: Huina
authors.initials: H
authors.lastname: Lu
authors.forename: Jianfei
authors.initials: J
authors.lastname: Fu
authors.forename: Hong
authors.initials: H
authors.lastname: Xiong
authors.forename: Aibin
authors.initials: A
authors.lastname: Liang
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D000068258:Bevacizumab; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects* / Q000235:genetics*; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D034622:RNA Interference / Q000187:drug effects; D034741:RNA, Small Interfering / Q000235:genetics; D016196:S Phase / Q000187:drug effects / Q000235:genetics; D020298:U937 Cells; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D034741:RNA, Small Interfering; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D003561:Cytarabine; D000068258:Bevacizumab; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2