Clinical Observation And Mechanism Of Lung Inhibitory Mixture Inhibiting Lung Adenocarcinoma Based On IL-6/PI3K/Akt/mTOR Pathway

Objective:To study the clinical efficacy of Lung Inhibitory Mixture on stage IIIB or IV lung adenocarcinoma patients,and to explore the anti-tumor mechanism of Lung Inhibitory Mixture through IL-6/PI3K/Akt/mTOR signaling pathway by animal and cell experiments.Methods: 110 patients with stage IIIB or IV lung adenocarcinoma who met the inclusion criteria were randomly divided into control group and treatment group with 55 cases in each group.Both groups were treated with standard western medicine.The control group was given AP(pemetrexed+cisplatin)chemotherapy.The treatment group was given Lung Inhibitory Mixture orally 100 ml,twice a day,on the basis of AP chemotherapy.The quality of life score,clinical symptom score,serum level of IL-6,Changes in tumor size,PFS,OS and incidence of adverse events between the two groups were observed.In animal study,To establish a lung cancer model in nude mice,human lung adenocarcinoma A549 cells were implanted into nude mice.Thirty-six successful nuding mice were randomly divided into six groups:saline group,lung inhibitory mixture low concentration group,lung inhibitory mixture medium concentration,lung inhibitory mixture high concentration group,cisplatin group and lung inhibitory mixture middle concentration group combined with cisplatin group.Each group had six mice(Preliminary experiments showed that the medium concentration group was the best one for lung inhibitory mixture).The nude mice were administered with Chinese medicine,cisplatin and saline daily.Once a day for 4 weeks.The anti-tumor rate of each group was observed;the level of IL-6 in blood was detected by Elisa;the expression of PI3 k,Akt,p-Akt,mTOR,S6K1,Bcl-2 and Bax in tumors were detected by Western Blot;and the expression ofIL-6,S6K1 and Bcl-2 was investigated by immunohistochemistry.Human lung adenocarcinoma A549 cells were selected as experimental objects in cell experiment.Observation of the proliferation of A549 cells inhibited by lung inhibitory mixture at concentrations of 10,20 and 30 ug/ml respectively by MTT;the level of IL-6was detected by Elisa.optimum concentration of traditional Chinese medicine group was screened according to drug safety considerations.The cells were divided into control group,lung inhibitory mixture group,cisplatin group and combination group.MTT,Transwell and Elisa methods were used to detect the proliferation,invasion and IL-6expression of A549 cells.Results:The clinical indicators showed that the combined group had significant advantages over the control group in terms of quality of life score,clinical symptom score,changes of IL-6 level in serum,PFS,ORR and incidence of adverse events after treatment(P<0.05),although the improvement of some tumors,total survival time(OS)and some safety indicators were alleviated compared with the control group,there was no statistical significance(P>0.05).Animal experiments showed that lung inhibitory mixture significantly inhibited the growth of tumors,and decreased the levels of IL-6,PI3 K,p-Akt,mTOR,S6K1 and Bcl-2,promoting Bax expression,The experiment proved that the combined group had the best effect,and the difference was statistically significant(P<0.05).In the cell experiment,the lung inhibitory mixture can reduce the level of inflammatory factors IL-6,inhibit cell proliferation and invasion,especially in the combined group.Conclusion: Clinical and experimental studies confirm that Lung Inhibitory Mixture can reduce the expression of IL-6,and experiments further verify that lung inhibitory mixture can increase Bax expression,reduce Bcl-2 level and inhibit cell proliferation by affecting IL-6/PI3K/Akt/mTOR/S6K1 pathway.