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The Mechanism Of Curcumin In The Treatment Of Esophageal Squamous Cell Carcinoma Based On Network Pharmacology

Posted on:2024-06-09Degree:MasterType:Thesis
Country:ChinaCandidate:J H DengFull Text:PDF
GTID:2544307145994199Subject:Biology
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The treatment of cancer patients is a major problem in the world today.Some existing anti-cancer chemotherapy drugs,such as platinum drugs,gemcitabine,5-fluorouracil,etc.,have been clinically resistant to drugs and decreased sensitivity to radiotherapy.In order to treat cancer patients,it is very necessary to develop new and effective anti-cancer drugs.In addition to showing targeting in anti-tumor,CUR can be derived from food,has low toxicity and is well tolerated by patients,and is considered as a safe compound,which indicates that CUR has the potential to become a new anticancer agent.In this study,two kinds of esophageal squamous cell cells Eca-109 and KYSE150 and normal esophageal epithelial cell line Het-1A were used as experimental materials.Following the research methods of network pharmacology,relevant targets of CUR and ESCC and important signaling pathways were found through the collection of biological information database data.Furthermore,experiments were conducted to verify the CUR’s influence on ESCC cell activity.At the same time,the CUR’s influence on related targets and signaling pathways of ESCC cells was verified,the possible biological mechanisms of CUR’s treatment of ESCC were explored,and important targets of CUR’s treatment of ESCC were found,providing experimental basis for the development of targeted drugs.To provide theoretical basis and experimental data for the clinical application of CUR.In this study,network pharmacology was used to collect the targets of curcumin and esophageal squamous cell carcinoma,and PPI was used to find the core target of curcumin acting on esophageal squamous cell carcinoma.KEGG analysis was performed on the core target to find the signal pathway enriched in the core target,namely,the core signal pathway,and the intersection genes of curcumin and esophageal squamous cell carcinoma were analyzed to understand their possible effects;The effects of curcumin on the activity,apoptosis,autophagy,invasion,migration and cell cycle of esophageal squamous cell carcinoma cells were detected by MTT assay,fluorescence staining,flow cytometry,scraping and Transwell.Molecular experiments were conducted to verify the effects of curcumin on core targets and core signaling pathways of esophageal squamous cell cells.m RNA expression of core targets was detected by q RT-PCR and protein expression of core targets and core signaling pathways was detected by Western blot.The results showed that: CUR can play a role in the treatment of ESCC through multi-targets,multi-signaling pathways and multi-pathways.CUR can block the cell cycle of ESCC cells,inhibit cell proliferation,migration and invasion,and promote cell apoptosis and autophagy.The main mechanism may be that CUR can regulate the PI3KAkt-p53 signaling pathway by down-regulating the m RNA and protein expression of core genes EGFR,APP and HSP90AA1,up-regulating the m RNA and protein expression of TP53,and down-regulating the protein expression of PI3 K,AKT and MDM2.
Keywords/Search Tags:Network pharmacology, Curcumin, Esophageal squamous cell carcinoma, PI3K-AKT-p53 signaling pathway
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