Study On The Distribution Of TCM Syndromes Of Glucose And Lipid Metabolism In Lung Cancer And Mechanism Of Toxin-attack Therapy Regulating Metabolic Reprogramming Network Of Lung Cancer

Objective: To study the distribution of TCM syndromes of glucose and lipid metabolism in patients with lung cancer.To find out its intrinsic pathogenesis and pathological factors.To verify the inhibition of drug nano realgar on metabolic reprogramming network of lung cancer,and to find its mechanism.Methods:(1)Clinical research: By making clinical questionnaires,we observed the relationship between the distribution of glucose and lipid metabolism index and TCM syndromes in patients with lung cancer and factors such as gender,age,pathological type,stage,course of disease,recurrence or metastasis,past treatment methods were also taken into consideration.We explored the relationship between glucose and lipid metabolism and TCM syndromes distribution,analyzed the intrinsic pathogenesis and pathological factors,and determined the appropriate target drugs.(2)In vitro experiments: MTT assay,plate clone formation assay,GOD assay,double antibody sandwich ELISA,Real-time PCR and Western blot were used to observe the inhibitory effect of target drugs on A549 lung cancer cells and theregulation of related metabolic enzymes,genes and proteins in the metabolic reprogramming network;(3)In vivo experiments: The inhibitory effect of target drugs on subcutaneous transplantation of lung cancer A549 cells in BALB/c-nu mice and the regulation of metabolic reprogramming network were observed by general conditions,body weight,blood sugar,tumorigenesis and other indicators of mice,as well as the results of HE staining colorimetry,double antibody sandwich ELISA,Real-time PCR and Western blot.Results:(1)The average blood sugar level of middle-aged and elderly patients,squamous cell carcinoma patients,patients undergoing surgery and chemotherapy was relatively higher(P<0.05);the average blood lipid level of middle-aged and elderly patients with long course of disease,late stage,recurrence and metastasis was relatively higher(P<0.05).The average blood sugar level of patients with phlegm-stasis-toxin syndrome,Qi-yin deficiency syndrome and spleen deficiency-phlegm-dampness syndrome was relatively higher(P<0.05),while the average blood lipid level of patients with spleen deficiency-phlegm-dampness syndrome,Yin deficiency-internal heat syndrome and Qi-yin deficiency syndrome was relatively higher(P<0.05).The syndrome of phlegm-stasis-toxin stagnation is common in all pathological types,stages and courses of middle-aged and old patients.The pathogenesis of abnormal glucose and lipid metabolism in lung cancer patients might be declared.Because of the deficiency of positive qi and the intrusion of pathogenic toxins,the movement of qi,blood and body fluid is blocked,resulting in stagnation of qi,phlegm and dampness,blood stasis and cancer toxicity.The abnormal metabolism of glucose and lipid is caused by the rampant cancer toxicity,and metabolic reprogramming occurs in tumors.Cancer toxicity is its intrinsic pathological factor.Toxin attack therapy and its representative drug nano realgar may have targeted inhibitory effect on metabolic reprogramming of lung cancer.(2)Nano realgar can inhibit the growth and proliferation of human lung cancer A549 cellsin vitro.After 24 hours of nano realgar intervention,IC50 was about 66.29ug/ml.Nano realgar can reduce intracellular glucose concentration,and inhibit the expression of metabolic enzymes GLUT1,PDK1,PFK1,PKM2,PDH and LDH related to the metabolic reprogramming regulatory network of A549 cells extensively.The mechanism may be that arsenic contained in nano realgar binds to thiol enzymes and forms arsenic complexes,resulting in inactivation of enzymes.It can down-regulate the expression of TP53?HIF-1? gene in A549 cells,inhibit the expression of PI3K/AKT/m TOR pathway node protein and HIF-1? protein in A549 cells,and lead to the inhibition of metabolic reprogramming regulatory network in a dose-and time-dependent manner.Besides,the downregulated TP53 gene might be a mutant.(3)Nano realgar can inhibit the growth of lung cancer A549 subcutaneously transplanted in BALB/c-nu mice in a dose-and time-dependent manner,induce necrosis and inflammation of subcutaneous transplanted tumors in a dose-dependent manner,inhibit the expression of metabolic reprogramming network-related enzymes GLUT1,PDK1,PFK1,PKM2,PDH and LDH in tumor tissues,and down-regulate the expression of TP53?HIF-1? gene in tumor tissues.The downregulated TP53 gene might be a mutant.It can inhibit the expression of PI3K/AKT/m TOR pathway node protein and HIF-1? protein in tumor tissues,thereby inhibiting the metabolic reprogramming network.There was no death in mice during gastric administration.The general situation was acceptable and the safety of drug application was acceptable.Conclusion:The distribution of TCM syndromes related to glucose and lipid metabolism in lung cancer patients shows that cancer toxin may be the intrinsic pathogenesis of abnormal glucose and lipid metabolism in lung cancer patients.Toxin attack therapy and its representative drug nano realgar can inhibit the metabolic reprogramming network of lung cancer,which may lead to a good inhibitory effect on lung cancer.Its mechanism may be related to inhibiting the expression of metabolicreprogramming-related enzymes GLUT1,PFK1,PKM2,PDH,LDH,down-regulating the expression of mutant TP53?HIF-1? gene,inhibiting the expression of PI3K/AKT/m TOR pathway node protein and HIF-1? protein.