Potential of Targeting PDE1C/2A for Suppressing Metastatic Ovarian Cancers
Abstract
ERK signaling pathway has long been suggested as a therapeutic target for ovarian cancer progression and metastasis. In our previous studies, we showed that 1) high Erk activity is sensitive to the elevation of intracellular cAMP concentration; and 2) agents elevating cellular cAMP suppresses growth of aggressive ovarian cancer cells. This proposal is sought to 1) understand molecular mechanisms associated with forskolin/PDE2 inhibitor-induced apoptosis of aggressive ovarian cancer cells and 2) to evaluate the translation value of treating aggressive ovarian cancer cells with forskolin and PDE2 inhibitor in anintraperitoneal xenograft model. In first year of the funding, we showed that knockdown of PDE2A rendered ovarian cancer cells susceptible for forskolin-induced cell growth inhibition/apoptosis. We further showed that combined use of forskolin and Bay60-7550 (PDE2 inhibitor) down regulates the levels of Bcl2, survivin and phosphorylated Akt whereas induces the expression of Bim1. The effect of forskolin/Bay60-7550 is clearly mediated by PKA because PKA inhibitor H89 abolishedgrowth inhibition caused by forskolin/Bay60-7550. Results from our first year study elucidate molecular mechanism underlying forskolin/PDE2 inhibitor-led ovarian cancer cell growth inhibition/apoptosis and built basis of testing forskolin/Bay60-7550 in ovarian cancer models.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2014
- Accession Number
- AD1012151
Entities
People
- Shuang Huang