Clinical Efficacy And Mechanisms Of Disodium Cantharide Injection In Non-small Cell Lung Cancer

Malignant tumor is one of the most fatal diseases in the world,and lung cancer is the most common respiratory tumor.lung cancer does not produce symptoms in Early stage,so it is difficult to find it in clinic.The vast majority of patients with lung cancer are in the middle and late stages of the disease,and they lose the opportunity of radical surgical treatment.Besides,the postoperative efficacy is poor,the recurrence rate is high,and the 3-year survival rate is less than 20%.In normal multicellular organisms,DNA damage causes abnormal changes in the expression of multiple genes and lead to the transformation of the target cells,after the process of heterogeneity,the cells acquire the ability to infiltrate and metastasize,thus forming what we call a malignant tumor.The ability to infiltrate locally and metastasize remotely is one of the major biological characteristics of tumors and one of the major causes of death in cancer patients.phosphoinositide-3 kinase(PI3K)-protein kinase B(AKT)-mammalian target of rapamycin(mTOR)Signaling pathway is closely related to tumor apoptosis,autophagy,metastasis and other aspects,which can become a new target for tumor treatment,with a broad application prospect.By inhibiting the PI3k/AKT/mTOR signaling pathway,tumor cell proliferation can be reduced,angiogenesis can be reduced,and tumor metastasis can be inhibited.Traditional Chinese medicine has a long history and a rich theoretical basis in The treatment of malignant tumors.Cantharides is the dry bulk of Mylabris phalerata Pallas or Mylabris cichorii Linnaeus.Its main component cantharidin is a common anti-tumor traditional Chinese medicine extract.The main component of Disodium Cantharide Injection is a small molecular derivative of cantharidin,which retains the medicinal efficacy of cantharidin and greatly reduces the toxic and side effects.It can be used for the treatment of a variety of tumors.A large number of clinical trials and experimental studies have shown that sodium cantharidate injection is suitable for the treatment of a variety of malignant tumors,and can reduce the expression of inflammatory factors and vascular endothelial growth factor,effectively inhibit the metastasis of malignant tumors,extend the survival period of patients,and improve the quality of life of patients.The main purpose of this paper is to observe the clinical efficacy of Disodium Cantharide Injection in the treatment of patients with non-small cell lung cancer,to investigate its effect on the invasion and metastasis of human lung cancer A549 cells,and to conduct a preliminary study on its mechanism.Clinical sample collection showed that Disodium Cantharide Injection could effectively inhibit the growth of lung cancer and improve the quality of life of patients.In vitro experimental results showed that,compared with the results of the control group,Disodium Cantharide Injection could inhibit the proliferation,invasion and metastasis of human lung cancer cells within a certain concentration rangeThis study is divided into two parts.Part I:Clinical efficacy of Disodium Cantharide Injection combined with chemotherapy in patients with non-small cell lung cancer.Objective:this study mainly collected clinical samples of patients with non-small cell lung cancer treated by sodium cantharidate injection,and summarized them from two aspects:efficacy evaluation and TCM syndrome evaluationMethods:We chose 48 patients with advanced non-small cell lung cancer in Yangzhou traditional Chinese medicine hospital from 2018 to 2019.Divided into two groups.The traditional Chinese medicine combined chemotherapy group contains 25 cases,14 cases of male,11 cases of female,mean age 64.84±2.87 years,for the Disodium Cantharide Injection+Cisplatin/Albumin paclitaxel treatment,The chemotherapy group contains 23 cases,the 13 cases of male,10 cases of female,average age 65.39±2.33,Cisplatin/Albumin paclitaxel treatment,there was no statistically significant difference between the two groups of patients in gender,age,etc.This paper summarizes the curative effect evaluation and TCM syndrome evaluation.Results:compared with the control group,the Treatment effect of TCM combined chemotherapy group was better than the chemotherapy group,and the TCM combined chemotherapy group had more obvious improvement in TCM syndromes compared with the chemotherapy group(P<0.05)Conclusion:Disodium Cantharide Injection combined with chemotherapy can enhance the curative effect of chemotherapy and improve the TCM symptoms of patientsPart II:To investigate the effects of Disodium Cantharide Injection on the metastasis and its molecular mechanism of human lung cancer A549 cells.Objective:To investigate the effect of Disodium Cantharide Injection on the metastasis ability of A549 cells,Detected the changes in PI3k/AKT/mTOR signaling pathway protein expression in cells,and preliminary explore its possible molecular mechanism in inhibiting the occurrence and development of lung cancer.Methods:The A549 cells of human lung cancer in logarithmic growth stage were taken.adding 5000 cells into each well.After cell adherence,100 ?L FBS10%medium for each well contained different concentrations of Disodium Cantharide Injection(0.3725,0.625,1.25,2.5,5 ?g/mL),with 5 parallel wells for each concentration.After 24h,48h and 72h,abandoned the supernatant,detected the OD value by MTT assey,and cell inhibition rate was calculated.In logarithmic phase of human lung cancer A549 cells,set Disodium Cantharide Injection treatment group(0.4,1.0 ?g/ml)and the positive control medicine group(DDP 2 mg/L),negative control group,after 24 h,detected Cell migration by cell scratch assay,Using Western blot assay to detect expression level of different protein(PI3k,and AKT,mTOR,P70 S6 and VEGF-C).Results:The migration and proliferation abilities of A549 cells can be inhibited by Disodium Cantharide Injection,and it is concentration-and time-dependent.After drug action,the expression levels of PI3k,AKT,mTOR,P70 S6,and VEGF-C proteins were reduced and showed a significant concentration dependenceConclusion:The proliferation and migration of A549 cells can be inhibited by Disodium Cantharide Injection and its molecular mechanism may be correlation with the repression of PI3k/AKT/mTOR signaling pathway related proteins.