Preliminary Study On Autophagy And Apoptosis Induced By Nifeviroc In A549 Cells Of Non-small Cell Lung Cancer

Background The most common malignant tumor in the world is lung cancer,and its morbidity and mortality rank the first among malignant tumors,among which non-small cell lung cancer accounts for the vast majority of lung cancer,the proportion is as high as90%.As the symptoms of lung cancer in the early stage are relatively mild,not easy to be found,there is no obvious non-symptoms,so most of the patients are found in the middle and advanced stage,only 30-40% of them are in the early middle stage,so most of the patients lost the opportunity for early radical treatment and the best opportunity for surgical treatment.At present,the treatment of lung cancer mainly includes surgical resection,chemoradiotherapy,immunotherapy and molecular targeted therapy.Although several treatments for lung cancer are becoming mature and each has its own advantages,there are still various challenges to be faced,and molecular targeting technology has unique targeting,efficacy and safety in tumor drugs.At present,the main problem about the clinical use of non-small cell lung cancer is that it is not easy to be found in the early stage,so the best treatment period is lost for surgical resection.Systemic chemotherapy can make people normal cells also have a certain killing effect,New immunotherapy may produce significantly different immune adverse reactions from chemotherapy drugs and traditional molecular-targeted drugs.Therefore,it is of great significance to study the molecular-targeted drugs for non-small cell lung cancer.In the early stage of the study,can be in the breast and non-small cell lung cancer,the expression of CCR5 quantity increased obviously,and studies that inhibit breast cancer cell CCR5 expression can make the breast cancer cells apoptosis,and in the lab can also get in earlier research,amount of CCR5 expression in non-small cell lung cancer also increases obviously,is obtained by the computer screen,Nifeviroc is a CCR5 inhibitor,at the same time,Nifeviroc to non-small cell lung cancer induced apoptosis.According to the relationship between CCR5 and tumor,the research on screening small-molecule targeted drugs against non-small cell lung cancer based on CCR5 will provide new ideas for the treatment of non-small cell lung cancer.Autophagy is a general term for the degradation of cytoplasmic components in lysosomes and plays an important role in the development of tumors.The occurrence of autophagy may promote the apoptosis of tumor cells so as to promote the occurrence and development of tumor cells.On the other hand,it may also inhibit the occurrence and development of tumor cells.Therefore,the study on the relationship between autophagy and apoptosis is a hot spot and focus of current tumor research.If we can better study the relationship between autophagy and the development of tumor cells,it will provide more useful clues for tumor treatment.Research objective In the early stage,based on CCR5,this laboratory verified that Nifeviroc could bind to CCR5 well through virtual screening,and the preliminary experiment also confirmed that Nifeviroc could effectively induce the apoptosis of non-small cell lung cancer cells A549.Based on the previous stage,this study further explored the mechanism of Nifeviroc inducing the apoptosis of A549 cells.On the other hand,autophagy plays an important role in the development of tumors.This study will also explore the relationship between autophagy and A549 cell apoptosis,laying a theoretical foundation for Nifeviroc as a small-molecule targeted drug in the treatment of non-small cell lung cancer.Research methods1.Firstly,with the help of computer-aided design,the Surflex Dock module of Sybly2.1 was used to carry out the molecular docking study between CCR5 and Nifeviroc,which further confirmed that the target of Nifeviroc action was CCR5 and further understood its action mode.2.Based on the results of previous studies on the induction of A549 cell apoptosis by Nifeviroc in the laboratory,the mechanism of Nifeviroc in inducing A549 cell apoptosis was further studied.3.To investigate whether Nifeviroc induced autophagy in A549 cells and to investigate the relationship between autophagy and apoptosis induced by Nifeviroc.4.To study the mechanism of autophagy induced by Nifeviroc in A549 cells in order to provide useful clues for the treatment of non-small cell lung cancer.Research results1.Nifeviroc can carry on the good and CCR5 crystal in computer simulation of docking.2.Nifeviroc can induce A549 cell autophagy occurs,and is induced by inhibition of PI3K/Akt/m TOR pathway.3.Nifeviroc treatment autophagy and apoptosis of A549 cells is promote each other.4.Nifeviroc induced A549 cell autophagy and CCR5 targets have certain relations.In summary,Nifeviroc can induce autophagy in A549 cells,and there is a mutually promoting relationship between autophagy and apoptosis induced by Nifeviroc in A549 cells.