Study On The Molecular Mechanism Of Small Molecular Inhibitor Against Lung Cancer Cells

Carcinoma of lung is a kind of high malignant degree of respiratory tract tumor,which is difficult to be diagnosed and treated.According to the published reports,the morbidity and mortality of lung cancer are increased significantly in recent 50 years.Its mortality and morbidity ratio take the first place of all the malignant tumor of men and the second place of women,which seriously threats to human health.The search for new agents for its treatment is of great importance.More than 25% human lung cancer is caused by ras mutation.Ras protein targeting therapy has become a research hotspot for anti pneumonic drug.In present study,the cytology and molecular biological technology were used to detect the inducing apoptotic,autophagic and cell cycle regulation effect associated with the suppression of cell viability of smallmolecule NSC290956 on K-ras mutation carcinoma cell lines NCI-H358 in vitro.Solutions presented in this thesis can be summarized as follows:-NSC290956 inhibited the proliferation of NCI-H358 cells by induction cell apoptosis.Caspase-3,caspase-9,Cytochrome C,ROS and Bax are involved in the inhibition effect of NSC290956.NSC290956 may increase ROS level of cells,upregulate Bax protein expression,decrease mitochondrial membrane potential and induce Cytochrom C in mitochondrial of cells release to cytosol,activate caspase reaction and then induce A549 and H358 cells apoptosis,and ultimately inhibit cells proliferation.-NSC290956 could restrain cells proliferation by attenuating the Raf/MEK/ERK signal pathway.-NCS290956 could induce apoptosis which is related to cell cycle arrest by flow cytometry and western blot.-NSC290956 could restrain H358 cells proliferation by inducing autophagy.