Hypoxia up-regulates the effects of prostaglandin E2 on tumor angiogenesis in ovarian cancer cells

Genhai Zhu, Ghassan M Saed, Gunter Deppe, Michael P Diamond, Adnan R Munkarah
Gynecologic Oncology 2004, 94 (2): 422-6

OBJECTIVE: Emerging evidence supports a role for prostaglandins (PG) and their synthesizing enzyme, cyclooxygenase (COX), in tumor angiogenesis. The objective of this study was to investigate the effects of prostaglandin E(2) (PGE(2)) on the expression of vascular endothelial growth factor (VEGF) and hypoxia-inducible transcription factor-1 alpha (HIF-1alpha) genes in epithelial ovarian cancer (EOC) cells.

METHODS: Two human EOC cell lines, MDAH-2774 and SKOV-3, were treated with exogenous dimethyl prostaglandin E(2) (dmPGE(2)) at two doses of 10 and 50 microg/ml and cultured for 24 h under both normoxic and hypoxic conditions. Total RNA was extracted from EOC cells with the use of a monophasic solution of phenol and GITC/Trizol method. The levels of COX-2, VEGF, and HIF-1alpha mRNA were measured by quantitative reverse transcription PCR (RT-PCR).

RESULTS: Under normoxic conditions, treatment of both ovarian cancer cell lines with dmPGE(2) resulted in a significant increase in VEGF expression but had no effect on HIF-1alpha. Culturing the cells under hypoxic conditions resulted in an increase in HIF-1alpha and VEGF mRNAs. The combination of hypoxia and dmPGE(2) treatment resulted in the highest levels of VEGF and HIF-1alpha when compared to either individual treatment.

CONCLUSION: PGE(2) is a potent stimulator of VEGF expression in ovarian cancer cells. This effect of PG is further potentiated under hypoxic conditions where it is also associated with a significant increase in HIF-1alpha expression.

Full Text Links

Find Full Text Links for this Article


You are not logged in. Sign Up or Log In to join the discussion.

Related Papers

Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"