The effects of the inhibition of inducible nitric oxide synthase on angiogenesis of epithelial ovarian cancer

John M. Malone, Ghassan M. Saed, Michael Peter Diamond, Robert J. Sokol, Adnan R. Munkarah

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Objective: The release of nitric oxide by tumor cells, through the stimulation of inducible nitric oxide synthase expression, may play a critical role in ovarian cancer progression. In this study we have sought to determine the effects of inhibiting inducible nitric oxide synthase on angiogenesis that was induced by 2 ovarian cancer cell lines, SKOV and MDAH2774. Study design: Real-time polymerase chain reaction and enzyme-linked immunosorbent assay techniques were used to determine the expression levels of inducible nitric oxide synthase and vascular endothelial growth factor in the ovarian cancer cell lines in response to treatments with l-NAME, an inhibitor of nitric oxide synthase, and SNAP, and nitric oxide donor. Ovarian cancer-induced angiogenesis was assessed in vitro with an established assay that is based on the ability of human umbilical vein endothelial cells to form a tubular network in response to angiogenic agents. Results: SKOV and MDAH2774 cell lines exhibited over-expression of inducible nitric oxide synthase and have high baseline nitric oxide levels. This was associated with high levels of vascular endothelial growth factor production and angiogenesis induction. Treatment of the ovarian cancer cell lines with l-NAME significantly reduced vascular endothelial growth factor levels production and completely inhibited angiogenesis. In contrast, treatment with SNAP significantly increased vascular endothelial growth factor levels and increased angiogenesis in both cell lines. Conclusion: Our data suggest that the inhibition of inducible nitric oxide synthase may form a basis for a novel therapeutic treatment option for ovarian cancer therapy.

Original languageEnglish (US)
Pages (from-to)1110-1116
Number of pages7
JournalAmerican Journal of Obstetrics and Gynecology
Volume194
Issue number4
DOIs
StatePublished - Apr 1 2006
Externally publishedYes

Fingerprint

Nitric Oxide Synthase Type II
Ovarian Neoplasms
Vascular Endothelial Growth Factor A
Cell Line
Nitric Oxide
Therapeutics
Immunosorbent Techniques
Nitric Oxide Donors
Human Umbilical Vein Endothelial Cells
Nitric Oxide Synthase
Ovarian epithelial cancer
Real-Time Polymerase Chain Reaction
Enzyme-Linked Immunosorbent Assay
Neoplasms

Keywords

  • Angiogenesis
  • Inducible nitric oxide synthase
  • Ovarian cancer
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Medicine(all)
  • Obstetrics and Gynecology

Cite this

The effects of the inhibition of inducible nitric oxide synthase on angiogenesis of epithelial ovarian cancer. / Malone, John M.; Saed, Ghassan M.; Diamond, Michael Peter; Sokol, Robert J.; Munkarah, Adnan R.

In: American Journal of Obstetrics and Gynecology, Vol. 194, No. 4, 01.04.2006, p. 1110-1116.

Research output: Contribution to journalArticle

Malone, John M. ; Saed, Ghassan M. ; Diamond, Michael Peter ; Sokol, Robert J. ; Munkarah, Adnan R. / The effects of the inhibition of inducible nitric oxide synthase on angiogenesis of epithelial ovarian cancer. In: American Journal of Obstetrics and Gynecology. 2006 ; Vol. 194, No. 4. pp. 1110-1116.
@article{00e60f2410e54eb7a3632d0354f0b631,
title = "The effects of the inhibition of inducible nitric oxide synthase on angiogenesis of epithelial ovarian cancer",
abstract = "Objective: The release of nitric oxide by tumor cells, through the stimulation of inducible nitric oxide synthase expression, may play a critical role in ovarian cancer progression. In this study we have sought to determine the effects of inhibiting inducible nitric oxide synthase on angiogenesis that was induced by 2 ovarian cancer cell lines, SKOV and MDAH2774. Study design: Real-time polymerase chain reaction and enzyme-linked immunosorbent assay techniques were used to determine the expression levels of inducible nitric oxide synthase and vascular endothelial growth factor in the ovarian cancer cell lines in response to treatments with l-NAME, an inhibitor of nitric oxide synthase, and SNAP, and nitric oxide donor. Ovarian cancer-induced angiogenesis was assessed in vitro with an established assay that is based on the ability of human umbilical vein endothelial cells to form a tubular network in response to angiogenic agents. Results: SKOV and MDAH2774 cell lines exhibited over-expression of inducible nitric oxide synthase and have high baseline nitric oxide levels. This was associated with high levels of vascular endothelial growth factor production and angiogenesis induction. Treatment of the ovarian cancer cell lines with l-NAME significantly reduced vascular endothelial growth factor levels production and completely inhibited angiogenesis. In contrast, treatment with SNAP significantly increased vascular endothelial growth factor levels and increased angiogenesis in both cell lines. Conclusion: Our data suggest that the inhibition of inducible nitric oxide synthase may form a basis for a novel therapeutic treatment option for ovarian cancer therapy.",
keywords = "Angiogenesis, Inducible nitric oxide synthase, Ovarian cancer, Vascular endothelial growth factor",
author = "Malone, {John M.} and Saed, {Ghassan M.} and Diamond, {Michael Peter} and Sokol, {Robert J.} and Munkarah, {Adnan R.}",
year = "2006",
month = "4",
day = "1",
doi = "10.1016/j.ajog.2005.12.019",
language = "English (US)",
volume = "194",
pages = "1110--1116",
journal = "American Journal of Obstetrics and Gynecology",
issn = "0002-9378",
publisher = "Mosby Inc.",
number = "4",

}

TY - JOUR

T1 - The effects of the inhibition of inducible nitric oxide synthase on angiogenesis of epithelial ovarian cancer

AU - Malone, John M.

AU - Saed, Ghassan M.

AU - Diamond, Michael Peter

AU - Sokol, Robert J.

AU - Munkarah, Adnan R.

PY - 2006/4/1

Y1 - 2006/4/1

N2 - Objective: The release of nitric oxide by tumor cells, through the stimulation of inducible nitric oxide synthase expression, may play a critical role in ovarian cancer progression. In this study we have sought to determine the effects of inhibiting inducible nitric oxide synthase on angiogenesis that was induced by 2 ovarian cancer cell lines, SKOV and MDAH2774. Study design: Real-time polymerase chain reaction and enzyme-linked immunosorbent assay techniques were used to determine the expression levels of inducible nitric oxide synthase and vascular endothelial growth factor in the ovarian cancer cell lines in response to treatments with l-NAME, an inhibitor of nitric oxide synthase, and SNAP, and nitric oxide donor. Ovarian cancer-induced angiogenesis was assessed in vitro with an established assay that is based on the ability of human umbilical vein endothelial cells to form a tubular network in response to angiogenic agents. Results: SKOV and MDAH2774 cell lines exhibited over-expression of inducible nitric oxide synthase and have high baseline nitric oxide levels. This was associated with high levels of vascular endothelial growth factor production and angiogenesis induction. Treatment of the ovarian cancer cell lines with l-NAME significantly reduced vascular endothelial growth factor levels production and completely inhibited angiogenesis. In contrast, treatment with SNAP significantly increased vascular endothelial growth factor levels and increased angiogenesis in both cell lines. Conclusion: Our data suggest that the inhibition of inducible nitric oxide synthase may form a basis for a novel therapeutic treatment option for ovarian cancer therapy.

AB - Objective: The release of nitric oxide by tumor cells, through the stimulation of inducible nitric oxide synthase expression, may play a critical role in ovarian cancer progression. In this study we have sought to determine the effects of inhibiting inducible nitric oxide synthase on angiogenesis that was induced by 2 ovarian cancer cell lines, SKOV and MDAH2774. Study design: Real-time polymerase chain reaction and enzyme-linked immunosorbent assay techniques were used to determine the expression levels of inducible nitric oxide synthase and vascular endothelial growth factor in the ovarian cancer cell lines in response to treatments with l-NAME, an inhibitor of nitric oxide synthase, and SNAP, and nitric oxide donor. Ovarian cancer-induced angiogenesis was assessed in vitro with an established assay that is based on the ability of human umbilical vein endothelial cells to form a tubular network in response to angiogenic agents. Results: SKOV and MDAH2774 cell lines exhibited over-expression of inducible nitric oxide synthase and have high baseline nitric oxide levels. This was associated with high levels of vascular endothelial growth factor production and angiogenesis induction. Treatment of the ovarian cancer cell lines with l-NAME significantly reduced vascular endothelial growth factor levels production and completely inhibited angiogenesis. In contrast, treatment with SNAP significantly increased vascular endothelial growth factor levels and increased angiogenesis in both cell lines. Conclusion: Our data suggest that the inhibition of inducible nitric oxide synthase may form a basis for a novel therapeutic treatment option for ovarian cancer therapy.

KW - Angiogenesis

KW - Inducible nitric oxide synthase

KW - Ovarian cancer

KW - Vascular endothelial growth factor

UR - http://www.scopus.com/inward/record.url?scp=33645851648&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645851648&partnerID=8YFLogxK

U2 - 10.1016/j.ajog.2005.12.019

DO - 10.1016/j.ajog.2005.12.019

M3 - Article

VL - 194

SP - 1110

EP - 1116

JO - American Journal of Obstetrics and Gynecology

JF - American Journal of Obstetrics and Gynecology

SN - 0002-9378

IS - 4

ER -