Targeted inhibition of VEGF-modulated survival and arsenic sensitivity in acute myeloid leukemia (AML).
Vascular endothelial growth factor (VEGF) is a specific growth factor for tumor-associated angiogenesis, and is also involved in leukemogenesis; however, its exact role in leukemia development remains elusive. In this study we used antisense oligonucleotide (AS) to manipulate VEGF function in acute myeloid leukemia (AML). HL60 and primary AML cells were transfected with VEGF AS (0.3 µmol/l). Cell proliferation and survival were assessed using the trypan blue exclusion assay. The viability of cells was determined using MTT. The IC50 values of arsenic trioxide (ATO) in HL60 cell were calculated by ICp software. The results showed that VEGF AS effectively inhibited AML cell proliferation and survival 72 hours post-transfection and exhibited time dependence. The IC50 value of ATO was significantly down-regulated by VEGF AS in HL60. Meanwhile, VEGF AS alone induced cell apoptosis, and promoted ATO-induced apoptosis. There is synergistic inhibitory effects between AS and ATO. VEGF AS down-regulated VEGF protein level in the supernatants and cellular VEGF mRNA level by western blot and real-time PCR. Therefore, targeted inhibition of VEGF suppressed survival and increased arsenic sensitivity in AML.
Department of Biochemistry and Molecular Biology, Medical College of Jinan University, Guangzhou, China.
Yong
Y
Ding
Xuejiao
X
Zhu
Yumin
Y
Li
Jia
J
Fei
Yuan
Y
Zhang
D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D004357:Drug Synergism; D020868:Gene Silencing; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D058990:Molecular Targeted Therapy; D016376:Oligonucleotides, Antisense / Q000235:genetics*; D010087:Oxides / Q000494:pharmacology*; D061251:Primary Cell Culture; D014162:Transfection; D014343:Trypan Blue; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors*
D001152:Arsenicals; D016376:Oligonucleotides, Antisense; D010087:Oxides; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D014343:Trypan Blue; D000077237:Arsenic Trioxide