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SKF95365 induces apoptosis and cell-cycle arrest by disturbing oncogenic Ca(2+) signaling in nasopharyngeal carcinoma cells
BACKGROUND: Aberrant modulation of store-operated calcium ions (Ca(2+)) entry promotes the progression of human malignancies. Previously, we reported that the blockage of store-operated Ca(2+) entry inhibited epidermal growth factor (EGF)-stimulated migration and distant metastasis in nasopharyngeal...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Dove Medical Press
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4629977/ https://www.ncbi.nlm.nih.gov/pubmed/26604781 http://dx.doi.org/10.2147/OTT.S92005 |
Sumario: | BACKGROUND: Aberrant modulation of store-operated calcium ions (Ca(2+)) entry promotes the progression of human malignancies. Previously, we reported that the blockage of store-operated Ca(2+) entry inhibited epidermal growth factor (EGF)-stimulated migration and distant metastasis in nasopharyngeal carcinoma (NPC) cells. However, the effects of pharmacological blocker on other Ca(2+) signaling-regulated malignant characteristics in NPC cells remained poorly understood. METHODS: We examined the effects of SKF96365, an inhibitor of store-operated Ca(2+) channel, on EGF-launched Ca(2+) signaling in two NPC cell lines. We determined the effects of SKF96365 on cell proliferation, colony formation, apoptosis, and cell-cycle status in vitro. We further elucidated the antitumor activity of SKF96365 in xenograft-bearing mice. RESULTS: It was found that SKF96365 disturbed the thapsigargin (TG)-stimulated Ca(2+) release from endoplasmic reticulum and the subsequent Ca(2+) influx. SKF96365 alone stimulated Ca(2+) responses merely due to endoplasmic reticulum-released Ca(2+). SKF96365 promoted cell mortality, inhibited colony formation, and induced apoptosis and cell-cycle arrest, while blunting the EGF-evoked Ca(2+) signaling. Furthermore, we confirmed that SKF96365 reduced NPC xenograft growth while activating caspase-7-related apoptotic pathway. CONCLUSION: SKF96365 exerts multiple antitumor activities through the distraction on the oncogenic Ca(2+) signaling transduction in NPC cells. |
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