Study On The Molecular Mechanism Of Synergistic Effect Of Luteolin And Other Active Ingredients Of Traditional Chinese Medicine On Lung Cancer

Lung cancer is a kind of tumor disease with high morbidity and mortality.Due to the high toxicity and side effects of conventional chemotherapy drugs and tumor resistance,the overall survival rate of lung cancer patients has not reached a satisfactory level.Therefore,new and effective treatment schemes need to be sought.At present,natural drugs have been widely concerned in the treatment of cancer.The combination of natural drugs can enhance the anti-cancer effect and reduce the side effects or drug resistance at the same time.In this paper,the effects and molecular mechanisms of luteolin combined with two natural drugs respectively,celastrol and quercetin,on lung cancer were investigated through network pharmacology and in vitro cell experiments.In this study,human non-small cell lung cancer cell line H157 was used as a model.Firstly,the synergistic drug combinations were screened by calculating the drug combination index,and then network pharmacology was used to predict the targets and signaling pathways of drug combinations.Finally,the anti-tumor mechanism of drug combinations was verified in vitro.The results showed that luteolin combined with celastrol or quercetin had a good synergistic effect on lung cancer.Through network pharmacological analysis,six core intersection targets of luteolin combined with celastrol and lung cancer were identified,including BCL2L1 and MMP9,and seven core targets of luteolin combined with quercetin including BCL2L1 and CASP3,and the relevant signaling pathway was PI3K-Akt pathway.In vitro experiments showed that luteolin and celastrol or quercetin synergously induced cell apoptosis,inhibited cell proliferation,migration and invasion,increased reactive oxygen species levels in vivo,and affected PI3K-Akt signaling pathway.In conclusion,this study demonstrated for the first time the synergistic effect and mechanism of luteolin combined with celastrol or quercetin on human non-small cell lung cancer cell line H157 in vitro,providing a new strategy for the treatment of lung cancer.