The Mechanism Of CHIR-99021 Inducing Apoptosis In A549 Cells

Lung cancer is the leading cause of cancer death in the world.Small cell lung cancer(SCLC)and non-small cell lung cancer(NSCLC)are two common types of lung cancer.And the proportion of non-small cell lung cancer is as high as 85%in lung cancer.Therefore,the research on the treatment of non-small cell lung cancer has been widely concerned.It has been found that CHIR-99021 can effectively induce apoptosis in non-small cell lung cancer cells,but its specific mechanism is still under study.During the conduction of Wnt/?-catenin signaling pathway,GSK-3? inactivates ?-catenin by phosphorylation or non-phosphorylation of ?-catenin.Since CHIR-99021 has an inhibitory effect on GSK-3?,apparently it is also an activator of Wnt/?-catenin pathway.GSK-3? has a dual role in the regulation of tumor formation,in other words,it can inhibit the formation of tumors,but it can also promote the formation of tumors.When its activity as a pro-tumor factor is suppressed,its anti-tumor effect is also blocked,as a result,Wnt/?-catenin signaling pathway is activated.In the study of the mechanism of tumorigenesis,activation of Wnt/?-catenin has been shown to promote tumorigenesis.Therefore,one of the challenges that must be overcome to achieve tumor therapy by inhibiting GSK-3? activity is to avoid activation of Wnt/?-catenin signaling pathway.In this study,we used A549 cells(human non-small cell lung cancer cell line)as a model cell to investigate the mechanism of apoptosis induced by CHIR-99021 in non-small cell lung cancer cells.And the effect of dose of CHIR-99021 on Wnt/?-catenin signaling pathway in A549 cells.The results showed that after treatment of A549 cells with 4?M CHIR-99021 for 24 hours,the activity of the Wnt/p-catenin signaling pathway in A549 cells can remain essentially unchanged.Moreover,at this dose,CHIR-99021 can up-regulate the expression of DR4 and DR5 by activating p53 in A549 cells,as a result,the TRAIL-induced apoptosis pathway is activated.At the same time,our study has further found that CHIR-99021 can block the NF-?B signaling pathway,and then hinder the formation of resistance to TRAIL-induced apoptosis in A549 cells.As a result,its efficiency in inducing apoptosis is increased.Therefore,the results of this study provide an important experimental basis for clinical treatment of non-small cell lung cancer with CHIR-99021 or its analogues.