Consistent with this, increased

levels of PTEN expression is considered as basic principle during reversal of resistance for tyrosine kinase inhibitors in patients with PTEN low-expression cancers. In order to improve PTEN expression, transfection by medium such as plasmid and virus is the common method in fundamental research [36–39]. However, in the clinical application, these methods DMXAA nmr have been unable to overcome its own errors and defects, for instance, transfection efficiency, https://www.selleckchem.com/products/mrt67307.html distribution in vivo, and so on. Finding the effective methods which can reverse primary drug-resistance in PTEN low-expression cells has become the urgent task on targeted therapy in clinical practice. As the drug resistant cell line for tyrosine kinase inhibitors due to low expression level of PTEN protein [18], H-157 cell line is the precondition of the experiment. Our results demonstrated that phospho-EGFR higher expression and low-expression of PTEN present in H-157 cells (Fig. 1), which are accorded with the reports of literatures [18]. We also observed

that when the H-157 cells were exposed to gefitinib, no significant deference of cell growth curve (Fig. 2), and no increase in the apoptosis of cells was found (Fig. 5). In conclusion, findings from the present study indicated that gefitinib has no effective antiproliferative function for H-157 cells. As a safe and satisfied method in the clinical therapy of cancer, Irradiation is easy to obtained, and it has not the disadvantages

such as maldistribution and low transfer efficiency Carnitine palmitoyltransferase II of transfection. Compared with selleck transfection, irradiation possesses incomparable superiority, and it is one of the best solutions of drug-resistant reversal for TKI therapy [40, 41]. Meanwhile, our results indicated that exposure to gefitinib after radiation enhanced the radiosensitivity of H-157 cells (Fig. 4). Considering that an increase in the level of the PTEN expression, the negative regulator of the phosphatidylinositol 3-kinase (PI3K) pathway was increased after irradiation, and then the second messenger PIP3 levels decreased, further activation of the serine/threonine kinase Akt/protein kinase B declined. So, the cell proliferation decreased and the cell death increased [29]. Therefore, x-ray radiation might play a major role in the drug-resistance reversal. It must point out that cross talk between different pathways makes miscellaneous of signal transductions in tumor cells. Up to now, it is still unclear that whether there exist other factors of PI3K pathway producing influence for tyrosine kinase inhibitors efficacy except for PTEN protein. Whether the factors are influenced by irradiation, and then made some effect on the drug-resistance further remains unknown. These all need further research on PI3K pathway.