The Study On The Mechanism Of Integrin β8 And Cisplatin Resistance In Non-small Cell Lung Cancer

Background and purposeLung cancer is the most common type of human malignant tumors in the world,and its morbidity and mortality rate rank first among malignant tumors and are increasing year by year.The main type of lung cancer is non-small cell lung cancer,accounting for about 85%.Currently,platinum-based drug combination chemotherapy is still a very important treatment for most patients with advanced or postoperative recurrence of non-small cell lung cancer.However,the cisplatin resistance rate of patients with non-small cell lung cancer remains high,which seriously affects the efficacy of cisplatin and the prognosis of patients,making it one of the main challenges facing the treatment of non-small cell lung cancer.Integrins exist on the surface of tumor cells and mediate the interaction between cells and cells and extracellular matrix,so they play an important role in the occurrence and development of malignant tumors.Nowadays,with the research on the mechanism of cisplatin resistance,integrins have also been shown to be related to the sensitivity of malignant tumors to cisplatin.Studies have reported that down-regulating the expression of ITGβ8 can increase the sensitivity of ovarian cancer cells to cisplatin.ITGβ8 is considered to be an important gene related to tumor metastasis.Its high expression can promote the proliferation,migration and invasion of malignant tumors,but its relationship with cisplatin resistance in non-small cell lung cancer has not been described.Therefore,this study aims to explore the relationship between ITGβ8 and cisplatin resistance in non-small cell lung cancer.Methods(1)Western Blot method to analyze the expression of ITGβ8 in human normal bronchial epithelial cell lines(HBE),human non-small cell lung cancer cell lines(H1299,A549,H1993)and human large cell lung cancer cell lines(H460,H661);(2)Construction of transfected cell line: use si RNA to transfect H1299 cells,construct ITGβ8 knockdown group H1299/si-ITGβ8 cell line and its negative control group H1299/si-NC cell line;(3)CCK-8 method to detect ITGβ8 on NSCLC The effect of cell proliferation ability and its effect on the sensitivity of NSCLC cells to cisplatin;(4)Cell scratch test and Transwell test to analyze the effect of ITGβ8 on the migration ability of NSCLC cells.Results(1)Western Blot results found that compared with the normal human bronchial epithelial cell line HBE,non-small cell lung cancer cell lines H1299,A549,H1993,H460 and H661 showed higher levels of expression of ITGβ8;(2)In cell proliferation experiments Among them,the proliferation ability of the cells in the ITGβ8knockdown group was significantly inhibited;(3)The cell scratch test and the Transwell experiment showed that the migration ability of the cells in the ITGβ8knockdown group was significantly reduced;(4)The cytotoxicity test results showed that the si-ITGβ8 group The IC50 of the cells was significantly lower than that of the negative control group.Conclusions(1)ITGβ8 is highly expressed in NSCLC cell lines;(2)knocking down ITGβ8 can reduce the proliferation ability of NSCLC cell lines;(3)knocking down ITGβ8 can inhibit the migration ability of NSCLC cell lines;(4)knocking down ITGβ8 can increase NSCLC Sensitivity of cell lines to cisplatin.