Verteporfin (VP) inhibits human retinoblastoma cell growth in vitro without light activation.

Abstract

Purpose: Verteporfin (VP), a benzoporphyrin derivative, is clinically used as a photosensitizer in photodynamic therapy for neovascular macular degeneration and ocular tumors. Recent studies indicate that VP may inhibit growth of tumor cells without photoactivation through inhibition of YAP-TEAD complex. In this study, we examined the effects of VP without light activation on human retinoblastoma Y79 and WERI cell growth in vitro.

Methods: Human retinoblastoma cell line Y79 and WERI was treated with VP. Cell growth was assessed by trypan blue exclusion test and MTT assay. Western blot analyses were performed to determine the expression of cell cycle regulators as well as potential YAP-TEAD downstream molecules and pathways such as mTOR/autophagy and Akt.

Results: VP treatment without light activation inhibited Y79 and WERI cell growth, proliferation and viability in a dose-dependent manner. VP increased doubling time and induced a mild G0/G1-phase cell cycle arrest and downregulation of cyclins. Treatment of retinoblastoma cells with VP was associated with downregulation of YAP-TEAD associated downstream signaling molecules. In addition there was an inhibition of mammalian target of rapamycin (mTOR) pathway, decreased phosphorylation of Akt.

Conclusions: VP without light activation is a potent inhibitor of cell growth in retinoblastoma Y79 and WERI cells and may provide a novel, non-chemotherapeutic approach for retinoblastoma treatment.

Keywords: 703 retinoblastoma • 744 tumors • 647 photodynamic therapy