Medical Oncology

, 33:73 | Cite as

Epac1 knockdown inhibits the proliferation of ovarian cancer cells by inactivating AKT/Cyclin D1/CDK4 pathway in vitro and in vivo

  • Meng Gao
  • Yanyan Ma
  • Robert C. BastJr.
  • Yue Li
  • Lu Wan
  • Yanping Liu
  • Yingshuo Sun
  • Zhenghui Fang
  • Lining Zhang
  • Xiaoyan WangEmail author
  • Zengtao WeiEmail author
Original Paper


Ovarian cancer is the leading cause of death among gynecological malignancies, and high grade serous ovarian carcinoma is the most common and most aggressive subtype. Recently, it was demonstrated that cAMP mediates protein kinase A-independent effects through Epac (exchange protein directly activated by cAMP) proteins. Epac proteins, including Epac1 and Epac2, are implicated in several diverse cellular responses, such as insulin secretion, exocytosis, cellular calcium handling and formation of cell–cell junctions. Several reports document that Epac1 could play vital roles in promoting proliferation, invasion and migration of some cancer cells. However, the expression levels and roles of Epac1 in ovarian cancer have not been investigated. In the present study, we detected the expression levels of Epac1 mRNA and protein in three kinds of ovarian cancer cells SKOV3, OVCAR3 and CAOV3. Furthermore, the effect of Epac1 knockdown on the proliferation and apoptosis of SKOV3 and OVCAR3 cells was evaluated in vitro and in vivo. The results showed that there was higher expression of Epac1 mRNA and protein in SKOV3 and OVCAR3 cells. Epac1 knockdown inhibited the proliferation of SKOV3 and OVCAR3 cells in vitro and in vivo. Decreased proliferation may be due to downregulation of Epac1-induced G1 phase arrest by inactivating the AKT/Cyclin D1/CDK4 pathway, but not to alterations in the MAPK pathway or to apoptosis. Taken together, our data provide new insight into the essential role of Epac1 in regulating growth of ovarian cancer cells and suggest that Epac1 might represent an attractive therapeutic target for treatment of ovarian cancer.


Epac1 Ovarian cancer cells Proliferation Cell cycle Apoptosis 



This work was supported by the National Natural Science Foundation of China (81471437, 81172863) and Natural Science Foundation of Shandong (ZR2012HM091, ZR2013HM105).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Meng Gao
    • 1
  • Yanyan Ma
    • 1
  • Robert C. BastJr.
    • 2
  • Yue Li
    • 1
  • Lu Wan
    • 1
  • Yanping Liu
    • 3
    • 4
  • Yingshuo Sun
    • 3
    • 4
  • Zhenghui Fang
    • 3
  • Lining Zhang
    • 1
  • Xiaoyan Wang
    • 1
    Email author
  • Zengtao Wei
    • 3
    • 4
    Email author
  1. 1.Department of ImmunologyShandong University School of MedicineJinanPeople’s Republic of China
  2. 2.Department of Experimental Therapeutics, Division of Cancer MedicineThe University of Texas MD Anderson Cancer CenterHoustonUSA
  3. 3.Department of Gynecology and ObstetricsJinan Central Hospital Affiliated to Shandong UniversityJinanPeople’s Republic of China
  4. 4.Department of Gynecology and ObstetricsShandong University School of MedicineJinanPeople’s Republic of China

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