Better understanding the molecular mechanisms controlling apoptosis is for that reason crucial to defining new targets for therapeutic intervention in lung cancer. Molecular genetic studies have ATP-competitive HSP90 inhibitor resulted in the discovery of a few potential targets for therapeutic style, such as PI3K and Akt. The PI3K signal transduction pathway was found to modify cell proliferation and survival and to be closely associated with the development and progression of numerous tumors. We and others have suggested that the PI3K signaling pathway is involved in early phase of lung cancer progression, increases in gene copy number of the PI3K catalytic subunit and increases in Akt activity, as detected by phosphorylation position, have been observed in premalignant and malignant human bronchial epithelial cells and in NSCLC cells. Downstream from PI3K, phosphorylated Akt is a Posttranslational modification effective promoter of cell survival inactivates and since it antagonizes various aspects of the apoptotic cascade such as proapoptotic Bad, caspase 9, and forkhead transcription factor family unit members. Various drugs targeted against changes in these pathways have been created and some are being tested for medical use within lung cancer. The apoptotic response caused by the inhibition of PI3K/Akt pathways have been seen to varying degrees in many types of cancer including NSCLC cells. Consequently, it’s important to establish mechanisms of sensitivity and resistance to these agents. Proteins of the Bcl 2 family are fundamental regulators of apoptosis. Over-expression of anti-apoptotic proteins like Bcl 2 and Bcl xL can offer tumor cells with resistance to various cellular insults including chemotherapeutic drugs in cell culture and in animal models. There is evidence for a link between the PI3K pathway and this survival mechanism. The PI3K pathway goals members of the Bcl 2 household Dub inhibitors through phosphorylation and functional regulation. The PI3K pathway also regulates the expression of these proteins, as PI3K/Akt stimulates the expression of anti-apoptotic Bcl 2 proteins, including Bcl xL and Mcl 1, through the activation of NF kB. Nevertheless whether Bcl 2 or Bcl xL plays a role in the resistance of lung adenocarcinoma cells to apoptosis induced by the inhibition of the pathway is not established. The present study was therefore made to examine the complete effect PI3K/Akt route and Bcl xL in preventing apoptosis in adenocarcinoma cells of the lung. We show that Bcl xL plays a vital role in mediating resistance of lung adenocarcinoma cells to cell death induced by the inhibition of the pathway. Mixed inhibition of Bcl xL and PI3K/Akt pathway might represent a helpful strategy for treating lung adenocarcinoma. Resources and Cell lines and culture problems Five human lung adenocarcinoma cell lines A549, H23, H1793, H549 and H441 were bought from the American Type Culture Collection.