Phytomedicine : international journal of phytotherapy and phytopharmacology · 2024
Securinine inhibits carcinogenesis in gastric cancer by targeting AURKA-β-catenin/Akt/STAT3 and the cell cycle pathway.
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Lv Caixia, Wang Yun, Kong Luke, Guo Jianghong, Chen Xiaoxia, Guo Fengtao, Dong Zhuanxia, Li Zhiyuan, Yang Xihua, Yang Mudan, Yang Wenhui, Li Feng, Zhang Huanhu
Аннотация
BACKGROUND: Gastric cancer (GC) is difficult to treat with currently available treatments. Securinine (SCR) has a lengthy history of use in the treatment of disorders of the nervous system, and its anticancer potential has been gaining attention in recent years. The aim of this study was to explore the repressive effect of SCR on GC and its fundamental mechanism.
METHODS: The efficacy of SCR in GC cells was detected by MTT assays. Colony formation, flow cytometry and Transwell assays were used to assess the changes in the proliferation, apoptosis, cell cycle distribution, migration and invasion of GC cells after treatment. AGS (human gastric carcinoma cell)-derived xenografts were used to observe the effect of SCR on tumor growth in vivo. The molecular mechanism of action of SCR in GC was explored via RNA sequencing, bioinformatics analysis, Western blotting, molecular docking, and immunohistochemistry.
RESULTS: SCR was first discovered to inhibit the proliferation, migration, and invasion of GC cells while initiating apoptosis and cell cycle arrest in vitro. It was also established that SCR has excellent anticancer effects in vivo. Interestingly, AURKA acts as a crucial target of SCR, and AURKA expression can be blocked by SCR. Moreover, this study revealed that SCR suppresses the cell cycle and the β-catenin/Akt/STAT3 pathways, which were previously reported to be regulated by AURKA.
CONCLUSION: SCR exerts a notable anticancer effect on GC by targeting AURKA and blocking the cell cycle and β-catenin/Akt/STAT3 pathway. Thus, SCR is a promising pharmacological option for the treatment of GC.
METHODS: The efficacy of SCR in GC cells was detected by MTT assays. Colony formation, flow cytometry and Transwell assays were used to assess the changes in the proliferation, apoptosis, cell cycle distribution, migration and invasion of GC cells after treatment. AGS (human gastric carcinoma cell)-derived xenografts were used to observe the effect of SCR on tumor growth in vivo. The molecular mechanism of action of SCR in GC was explored via RNA sequencing, bioinformatics analysis, Western blotting, molecular docking, and immunohistochemistry.
RESULTS: SCR was first discovered to inhibit the proliferation, migration, and invasion of GC cells while initiating apoptosis and cell cycle arrest in vitro. It was also established that SCR has excellent anticancer effects in vivo. Interestingly, AURKA acts as a crucial target of SCR, and AURKA expression can be blocked by SCR. Moreover, this study revealed that SCR suppresses the cell cycle and the β-catenin/Akt/STAT3 pathways, which were previously reported to be regulated by AURKA.
CONCLUSION: SCR exerts a notable anticancer effect on GC by targeting AURKA and blocking the cell cycle and β-catenin/Akt/STAT3 pathway. Thus, SCR is a promising pharmacological option for the treatment of GC.
Предметные рубрики MeSH
Stomach NeoplasmsHumansSTAT3 Transcription FactorAurora Kinase ACell Line, TumorAnimalsbeta CateninAzepinesProto-Oncogene Proteins c-aktHeterocyclic Compounds, Bridged-RingApoptosisCell ProliferationCell MovementMice, NudeDioxolanesMice, Inbred BALB CMiceAntineoplastic Agents, PhytogenicCell CycleSignal TransductionXenograft Model Antitumor AssaysCarcinogenesisMolecular Docking SimulationLactonesPiperidines