281P - Silibinin inhibits proliferative and invasive properties of human ovarian carcinoma cells OVCAR8 and SKOV3 through suppression of HRG/HER3 pathway

Date 20 December 2015
Event ESMO Asia 2015 Congress
Session Poster presentation 2
Topics Ovarian Cancer
Basic Science
Presenter Sepehr Javadikooshesh
Citation Annals of Oncology (2015) 26 (suppl_9): 80-84. 10.1093/annonc/mdv525
Authors S. Javadikooshesh1, M. Momeny1, G. Zarrinrad1, H. Yousefi1, A. Poursheikhani1, P. Sabouri1, M. Yaghmaie1, K. Alimoghaddam1, A. Ghavamzadeh1, J. Tavakkolibazzaz2, S.H. Ghaffari1
  • 1Hematology/oncology And Stem Cell Transplantation Research Center, Shariati Hospital, School Of Medicine, Tehran University Of Medical Sciences, Tehran, Iran, HORC-SCT, TUMS-Shariati Hospital, 4112 - Tehran/IR
  • 2Medical Genetics, Tehran University of Medical Sciences, 4112 - Tehran/IR

Abstract

Aim/Background

Epithelial ovarian cancer (EOC) is the most fatal gynecological malignancy due to its high proliferative and invasive capacities. A Heregulin (HRG)/HER3 autocrine loop increases proliferative and metastatic properties of EOC cells, suggesting that modulators of this signaling pathway may prove effective to trammel growth and motility of these cells. This study aimed to evaluate the effects of non-toxic multi-tyrosine kinase inhibitor silibinin on the proliferative and invasive characteristics of EOC cell lines OVCAR8 and SKOV3 through suppression of the HRG/HER3 signaling.

Methods

The effects of silibinin on proliferation, DNA synthesis, clonogenicity, cell cycle progression, cathepsin B enzymatic activity and migration and invasion were explored in vitro. To investigate the effects of silibinin on HRG/HER3 pathway, ELISA of secreted HRG in the medium and western blot of HRG/HER3/AKT/survivin pathway were analyzed.

Results

Silibinin suppressed proliferation, DNA synthesis and clonogenic abilities of OVCAR8 and SKOV3 cells via inhibition of the autocrine HRG/HER3 circuit. Silibinin-mediated attenuation of the HER3 signaling resulted in disabling the HER3/AKT/survivin axis and thereby, induction of G1/S cell cycle arrest. Furthermore, silibinin reduced invasive potentials of the EOC cells through quelling the HRG/HER3 pathway and suppression of cathepsin B activity.

Conclusions

Altogether, these results suggest that silibinin is a potential anti- cancer drug to inhibit proliferative and invasive characteristics of the EOC cells that exhibit an autocrine HRG/HER3 pathway.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.