The Study On Apoptosis Induction Mechanisms Of Proteasom Inhibitor MG132Promoting DDP In Non-small Cell Lung Cancer

BackgroundWith the rapid social development and gradual environmental deterioration,deteriorated environment is one of the important reasons which induce malignanttumors.The Investigations indicate that the malignant tumors at present are one of themost incidence rate and death rate of the diseases in the world.But the incidence rateof lung cancer locates the first place in the malignant tumors recently. So we paymore attention to how to cure the lung cancer effectively.The remedy of lung canceris at a new stage of comprehensive remedy which combine some methods such assurgery, chemotherapy, radiotherapy, biotherapy, targeted therapy.Although cuttingaway the tumor by surgery is the most principal and effective way.It is too late to getthe chance of early detection,because the lung cancer patients at early stage don’thave obvious clinical symptoms.When the patients who have symptoms come thehospital,50%-60%of the patients are already at the last stage(Ⅲ∕Ⅳ).The patientslose the best opportunities of surgery at that moment.So chemotherapy andradiotherapy is very important to the patients at the last stage.Because of the widelyuse of chemotherapy drugs at remedy of lung cancer, the toxic and side effect ofchemotherapy drugs and chemotherapy resistance are the obstacles which clinicians can’t conquer.The occurrence of cancer is mainly due to the gene mutation of thecell’DNA. Therefore,that finding the new target spot which can reduce thechemotherapy resistance of tumor,improve the chemotherapy drugs’effect and hasfew toxic and side effort has already been the hot spot of the medical discussion andstudy.The proteasome which exists widely in eukaryotic organism can selectivelydegrades cell protein and mediate various cell processes such as the process andupdate of protein, cell cycle,signal transmission,cell differentiation and apoptosis. Theproteasome inhibitor can inhibit the degradation of protein and induce cell apoptosisby interrupting the proteasome pathway. Hence,the proteasome inhibitor can inhibitthe gradation of protein of tumor cells,regulate cell cycle,inhibit growth andproliferation of tumor cells and induce apoptosis.There is few studies on whether itcan improve the killing effect and the sensitivity of chemotherapy drugs on tumorcells by the proteasome inhibitor combined with chemotherapy drugs.Therefore,inthis study the proteasome inhibitor combined with cisplatin induce apoptosis of thelung cancer A549,then analyzing the effect of the proteasome inhibitor to cellapoptosis.This study provides the experimental evidence of reducing the resistanceand improving the sensitivity of chemotherapy on tumor cells.ObjectiveTo explore the effect of apoptosis of the proteasome inhibitor combined withcisplatin on lung cancer A549and provide experimental evidence for further researchof the sensitivity of chemotherapy on tumor and improving chemotherapy efficacy.MethodsInhibition rates of the lung cancer A549intervened by different groups weretested by CCK-8.The morphological changes of cells and staining positive cells’ratewere detected by Hochest33342staining.The cells apoptosis rates were examined byflow cytometry.The expression of NF-κB and the apoptosis-related factors caspase9were measured by Western blot analysis. ResultThe inhibition rate of the groups of MG132or DDP were increasing with theincrease of time and concentration.Cell nucleus splitting and chromatin were found inthe cells.The cell apoptosis rate was also increasing.The apoptosis rate of cells treatedwith MG132and DDP was obviously increased than that alone treated with DDP. Theexpression of NF-κB was significantly decreased and the expression of the apoptosis-related factor caspase9of the combining group was significantly up-regulated thanthat alone treated with DDP.ConclusiveThe proteasome inhibitor MG132combined with DDP can apparently increasethe apoptosis rate.Part of the mechanism is that the proteasome inhibitor MG132inhibit the release of NF-κB of tumor cells,increase the sensitivity of tumor cells toapoptosis which was induced by DDP.It can further enhance the activation andexpression of the apoptosis-related factor caspase9.