半枝莲种素抗结直肠癌作用机制的生物信息学分析与实验验证

目的 结合生物信息学分析与体内、外实验探索半枝莲种素抗结直肠癌的作用及机制。方法 利用药物与疾病相关公共数据库分别获得半枝莲种素和结直肠癌的相关靶点,对二者交集靶点进行蛋白相互作用分析和功能富集分析以构建“药物-疾病”调控网络;利用机器学习算法筛选核心基因,并进行分子对接验证;利用人结肠癌细胞系(HCT116)开展细胞实验,验证半枝莲种素体外抗结直肠癌的作用;利用裸鼠皮下瘤模型验证半枝莲种素体内抗结直肠癌作用并探索相关分子机制。结果 共获得246个半枝莲种素药物靶点和3 658个结直肠癌相关靶点,利用50个交集基因构建了蛋白相互作用网络和“药物-疾病”调控网络。通过机器学习算法筛选出5个半枝莲种素抗结直肠癌的核心靶点。分子对接结果显示,所有核心靶点与半枝莲种素间的结合能均低于-5 kcal/mol。细胞实验显示,半枝莲种素处理组HCT116细胞的增殖、迁移及侵袭能力较对照组更弱。动物实验显示,半枝莲种素处理组裸鼠的皮下异种移植瘤生长速度较对照组更慢,且肿瘤组织中MET和磷酸化AKT的表达水平更低(P<0.05)。结论 半枝莲种素可通过下调MET的表达,影响PI3K/AKT通路的磷...

Bioinformatics analysis and experimental verification of the anti colorectal cancer mechanism of Banzhilian seed extract

Objective To explorethe anti-colorectal cancer effect and mechanism of rivularin by combining the analysisofbiological information and in vitro and in vivo experiments.Methods The targets of rivularin and colorectal cancer wereobtained by using the public databases related to drugs and diseases.The protein interaction and functional enrichmentanalysis of theintersecting targets were carried out to construct the "drug-disease"regulation network.The hub genes werescreened by machine learning tools and further validation was made through molecular docking method.Cell experimentswere conducted by using the human colon cancer cell line HCT116 to verify the anti-colorectal cancer effect of rivularin invitro.The subcutaneoustumor models in nude mice were utilized to validate the anti-colorectal cancer effect of rivularin inviwo and explore the relevant molecular mechanisms.Results In total,246 drug targets of rivularin and 3658 related targetsof colorectal cancer were obtained.The 50 intersecting genes were used to create the protein interaction and "drug-disease"regulation networks.Five hub targets of the anti-colorectal cancer effect of rivularin were screened by machine learningalgorithms.The molecular docking outcomes revealed that the binding energies between all hub targets and rivularin wereless than-5 kcal/mol.Cell experiments showed that the proliferation,migration,and invasion abilities of HCT116 cells inthe rivularin treatment groupwere weaker than those in the control group.Animal experiments showed that thegrowth ratesof subcutaneous xenograft tumors in nude mice in therivularin treatment groups were slower than those in the control group,and the expression levels of mesenchymal-epithelial transition factor(MET)and phosphorylated serine/threonine proteinkinase B(AKT)in tumor tissueswerealso lower(P<0.05).Conclusion Rivularin can exertits anti-colorectal cancer effectby downregulating MET expressionand affecting the phosphorylation status of the PI3K/AKT pathway.