5-Aminoisoquinolinone reduces the expression of vascular endothelial growth factor-C via the nuclear factor-κB signaling pathway in CT26 cells.
OBJECTIVE
VEGF-C has recently been identified as a key molecule which is involved in tumor lymphangiogenesis. The aim of this research was to investigate the role of PARP-1 inhibition in the regulation of VEGF-C expression in CT26 cells.


METHODS
CT26 cells were treated with or without the PARP-1 inhibitor 5-aminoisoquinolinone (5-AIQ). The expression of PARP-1, NF-kB, and VEGF-C proteins in CT26 cells was measured by Western blot analysis and the VEGF-C mRNA level was determined by reverse transcription polymerase chain reaction (RT-PCR). CT26-secreted VEGF-C was detected by enzyme-linked immunosorbent assay (ELISA).


RESULTS
The results of Western blot analysis showed that the expression levels of PARP-1, NF-kB, and VEGF-C were reduced in 5-AIQ treated CT26 cells and the levels of VEGF-C mRNA in 5-AIQ treated CT26 were significantly lower than t in 5-AIQ-untreated cells (P<0.05). The concentrations of CT26-secreted VEGF-C were also dramatically decreased (P<0.05).


CONCLUSIONS
Here, we provide evidence for the first time that PARP-1 inhibition dramatically reduces VEGF-C expression via the nuclear factor NF-kB signaling pathway. We therefore propose that PARP-1 inhibition has an anti-lymphangiogenic effect and may contribute to the prevention of metastatic dissemination via the lymphatic system.
Department of Pathology, Molecular Medicine and Cancer Research Center, Chongqing Medical University, Chongqing, China.
Wei-Qiang
WQ
Wu
Nilufer Jasmine Selimah
NJ
Fauzee
Ya-Lan
YL
Wang
D000818:Animals; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms; D007546:Isoquinolines / Q000494:pharmacology*; D042583:Lymphangiogenesis / Q000187:drug effects*; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis / Q000378:metabolism*; D000071137:Poly (ADP-Ribose) Polymerase-1; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D015398:Signal Transduction; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*
C411425:5-aminoisoquinolinone; D007546:Isoquinolines; D016328:NF-kappa B; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D042582:Vascular Endothelial Growth Factor C; C467483:vascular endothelial growth factor C, mouse; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases