PARP-1 may be involved in angiogenesis in epithelial ovarian cancer.

Abstract

Poly (ADP-ribose) polymerase 1 (PARP-1) is involved in DNA repair and has been implicated in chemoresistance. The present study investigated whether PARP-1 promotes angiogenesis in ovarian cancer. PARP-1 and vascular endothelial growth factor A (VEGF-A) expression and CD34+ microvascular density (MVD) were assessed using immunohistochemistry in 60 human epithelial ovarian cancer specimens. PARP-1 was stably knocked-down in SKOV3 cells using a specific small interfering RNA (siRNA); angiogenic capacity was assessed using the human umbilical vein endothelial cell (HUVEC) tubule formation assay; and PARP-1 and VEGF-A expression were examined by reverse transcription-quantitative polymerase chain reaction, western blotting and ELISA. PARP-1 was found to be expressed in 73.3% (44/60) of the human epithelial ovarian cancer specimens and was significantly associated with VEGF-A, MVD, tumor size, histological grade and lymphatic metastasis (P<0.05). Compared with cells transfected with a negative control siRNA, knockdown of PARP-1 significantly suppressed the ability of SKOV3 cell-conditioned media to promote HUVEC tubule formation on Matrigel in vitro. Knockdown of PARP-1 in SKOV3 cells also significantly reduced VEGF-A mRNA and protein expression and secretion. In summary, PARP-1 is overexpressed and may enhance angiogenesis in epithelial ovarian cancer by upregulating VEGF-A.