基于网络药理学和动物实验探讨克班宁纳米粒治疗非小细胞肺癌的作用机制OA

Aim To investigate the Mechanism of cre-banine nanoparticles(Cre-NPs)in treatment of non-small cell lung cancer(NSCLC)based on network pharmacology and animal experiments.Methods The related targets of crebanine(Cre)and NSCLC were searched in the related database of network phar-macology,and the"active ingredient-intersection tar-get"and protein interaction PPI network diagram was constructed.GO enrichment and KEGG pathway en-richment analysis were performed on the intersection targets,and molecular docking was performed on the key targets.The subcutaneous tumor-bearing mouse model of M109 lung cancer was established and di-vided into the control group,model group,cisplatin(2 mg ∙ kg-1)group,and Cre-NPs low,medium and high dose(2,4,6 mg∙kg-1)groups.The changes of body weight and tumor volume in mice were moni-tored.The relative tumor proliferation rate(T/C),tumor inhibition rate(TGI),thymus index and spleen index were calculated.The number of immune cells and liver and kidney function in mice were assessed using blood routine and serum biochemistry.The pathological changes,Ki67,CD31 protein expression and apoptosis of tumor tissues were detected using HE,IHC and TUNEL staining.The expression of PI3K/Akt/mTOR signaling pathway and apoptosis-related proteins in tumor tissues was detected by West-ern blot.Results Network pharmacology screened 125 Cre targets,1 682 NSCLC disease targets,and 48 intersection targets.KEGG analysis showed that PI3K/Akt signaling pathway may be the main pathway of Cre against NSCLC.Molecular docking showed that Cre had a strong binding force with the key proteins PI3K,Akt and mTOR in this pathway.The T/C≤60％and TGI≥40％of each administration group were effective in anti-tumor.Compared with the control group,the spleen index and the number of immune cells in the Cre-NPs low,medium and high dose groups signifi-cantly increased(P<0.05,P<0.01).There was no significant difference in the detection indexes of liver and kidney function(P>0.05).Compared with the model group,the tumor tissue of each administration group had different degrees of necrosis,and the ex-pression of Ki67 and CD31 protein decreased,and the apoptosis increased.Cre-NPs decreased the expres-sion of PI3K,p-PI3K,Akt,p-Akt,mTOR and p-mTOR(P<0.05,P<0.01),decreased the expres-sion of Bcl-2(P<0.01),and increased the expres-sion of Bax,caspase-9 and caspase-3(P<0.05,P<0.01).Conclusions Cre-NPs can effectively inhibit the growth of lung cancer in subcutaneous tumor-bearing mice,and its mechanism may be related to the regulation of PI3K/Akt/mTOR signaling pathway and the promotion of apoptosis.