NPS-2143 suppresses malignant phenotypes of retinoblastoma cells involved in regulating NF-κB pathway

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• The calcium-sensing receptor (CaSR) plays a role in various cancers.
• The specific function of CaSR and its antagonist NPS-2143 in human retinoblastoma remains uninvestigated.
• Understanding these mechanisms could reveal new therapeutic targets for retinoblastoma.

Purpose of the Study:

• To investigate the anti-retinoblastoma effects of NPS-2143.
• To elucidate the underlying molecular mechanisms, focusing on CaSR and NF-κB signaling pathways.
• To evaluate NPS-2143's potential as a therapeutic agent for retinoblastoma.

Main Methods:

• Cell viability was assessed using the cell counting kit-8 assay.
• Apoptosis was detected via flow cytometry.
• Western blotting was employed to analyze protein expression, including p-P65 NF-κB and p-IκBα.
• Small interfering RNA (siRNA) was used to reduce CaSR expression.
• Bortezomib was utilized to suppress the NF-κB pathway.

Main Results:

• NPS-2143 (16.5 µM) suppressed Y-79 cell proliferation and increased apoptosis.
• NPS-2143 treatment inhibited the protein levels of p-P65 NF-κB and p-IκBα.
• siRNA-mediated CaSR knockdown decreased Y-79 cell proliferation and enhanced apoptosis, also reducing p-P65 NF-κB and p-IκBα expression.
• Bortezomib treatment increased Y-79 cell apoptosis, while CaSR overexpression suppressed it.

Conclusions:

• NPS-2143 effectively inhibits retinoblastoma cell viability and induces apoptosis.
• The anti-retinoblastoma effect of NPS-2143 is mediated through the modulation of CaSR and NF-κB signaling pathways.
• NPS-2143 demonstrates potential as a therapeutic agent for human retinoblastoma.