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Period circadian regulator 3 (PER3) enhances sensitivity to radiotherapy in gastric cancer via Wnt/β-catenin pathway
Abstract
Purpose: To investigate a novel radiotherapeutic biomarker for gastric cancer (GC) treatment.
Methods: Radioresistant gastric cancer cells (NCI-N87-RR and MKN45-RR) were established using Gy. Protein levels were determined using western blots. Clone formation was evaluated and cell viability assessed by cell counting kit-8 (CCK-8). Apoptosis was determined by flow cytometry.
Results: Period circadian regulator 3 (PER3) was down-regulated in both cell lines (NCI-N87-RR and MKN45-RR). Moreover, PER3 over-expression enhanced sensitivity to radiation in radioresistant gastric cancer cells. Cell proliferation was inhibited, while PER3 promoted cell apoptosis. Furthermore, PER3 over-expression suppressed β-catenin and cellular myelocytomatosis oncogene (c-myc) and enhanced axin protein level induced by Gy, regulating transduction of Wnt/β-catenin signaling. In addition, PER3 contributed to the sensitivity of drug-resistant GC cells to cisplatin.
Conclusion: Period circadian regulator 3 enhances the sensitivity of GC to radiation through Wnt/βcatenin signaling pathway, providing a potential therapeutic strategy for the management of GC.