Blockade of sonic hedgehog signaling decreases viability and induces apoptosis in retinoblastoma cells: The key role of the PI3K/Akt pathway.

Abstract

Retinoblastoma (RB) is the most common type of malignant intraocular cancer in teenagers. One of the proteins abnormally expressed during oncogenesis of RB is sonic hedgehog (SHH), which possesses the capability to selectively activate transcription factors of different genes. However, the detailed function of SHH in RB remains unknown. Thus, the present study sought to investigate the role of SHH in the development of RB. The human RB WERI-Rb-1 cell line was used as an in vitro model for the knockdown of SHH by a specific short hairpin RNA (shRNA). To assess the effect of SHH inhibition on cell growth and apoptosis, cell viability, colony formation and flow cytometry assays were conducted. WERI-Rb-1 cells transfected with an shRNA targeting SHH were treated with the phosphoinositide-3 kinase (PI3K)/Akt agonist insulin-like growth factor 1 (IGF-1) to investigate the possible mechanism by which SHH promotes RB. The present results revealed that the silencing of SHH induced G1 cell-cycle arrest and apoptosis in WERI-Rb-1 cells and led to a decrease in cell viability, indicating that SHH has a critical role in the determination of RB cell survival. Moreover, according to the results of the IGF-1 assays, suppression of PI3K/Akt was a prerequisite for SHH inhibition, illuminating its potential role in the treatment of RB. The findings outlined in the present study elucidate a clear link between SHH and the PI3K/Akt pathway in RB cell survival, which could provide valuable inspiration for the advancement of therapies against RB.