RESUMO
OBJECTIVE: Salivary glands are frequently damaged in patients undergoing radiotherapy for head and neck cancer. Whether PANoptosis, which is characterized by pyroptosis, apoptosis, and necroptosis, occurs during radiation injury to the salivary glands and its role remain unclear. MATERIALS AND METHODS: Radiation-induced injury models of mouse submandibular gland, as well as primary acinar cells and HSG cell lines were established to determine the presence of radiation-induced PANoptosis. Several programmed cell death inhibitors, PFTα, disulfiram, Nec-1 and zVAD, were used to compare the effects of different cell death pathway on radiation injury. The LEGENDplex™ Human Inflammation Panel was used to characterize the inflammatory landscape secreted by salivary gland cells after radiotherapy. RESULTS: Single 15Gy or 8Gy radiotherapy triggered PANoptosis in mouse submandibular gland or salivary gland cells. Compared to the suppression of pyroptosis, apoptosis, or necroptosis alone, the inhibition of PANoptosis is more effective in preventing radiation injury to the salivary glands (p < 0.0001). The levels of multiple inflammatory cytokines were significantly up-regulated in the supernatants of HSG cells within 48 h after IR. Neutralizing inflammatory cytokines are capable of inhibiting salivary glands PANoptosis. CONCLUSIONS: Inhibition of PANoptosis induced by inflammatory cytokines can effectively prevent radiation injury of salivary glands.
RESUMO
OBJECTIVE: This study elucidated the clinical significance, functions, and mechanism of action of spindle and kinetochore-associated complex 3 (SKA3) in oral squamous cell carcinoma (OSCC). STUDY DESIGN: The SKA3 levels within the patients with OSCC were determined using the The cancer genome atlas (TCGA) database and clinical samples. The functions of SKA3 in OSCC cells were evaluated by cell counting Kit-8 (Beyotime Biotechnology, Haimen, China), 5-ethynyl-2'-deoxyuridine, wound healing, transwell invasion, flow cytometry, and xenograft nude mice model assays. A quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot were performed to assess mRNA and protein expression levels in specimens and cells, respectively. RESULTS: The SKA3 was highly expressed in OSCC tissues, and its knockdown suppressed OSCC cell proliferation, migration, and invasion, and promoted their apoptosis. Mechanistically, SKA3 was shown to modulate OSCC cell proliferation and apoptosis via the PI3K/AKT/GSK3ß and PI3K/AKT/FOXO1 pathways. CONCLUSIONS: Biologically, SKA3 has a potential carcinogenic role in OSCC progression and is a promising prognostic biomarker and therapeutic target.
