More Or Less Everything People Know About tuclazepam Is Wrong
The interaction of COX-2 and EGFR play an important role in tumour development and progression. Previous studies had shown that combined use of COX-2 inhibitor XAV-939 price celecoxib and EGFR tyrosine kinase inhibitors (TKIs) may have synergistic inhibitory effect on the proliferation of EGFR mutation cell lines. In this study, we explored the role of celecoxib and relevant signalling pathway in acquired gefitinib resistance in NSCLC. Methods:?Gefitinib-resistant PC9/G cell lines was induced by exposure of PC9 cell lines to MNNG and gefitinib and maintained in the media containing 0.05?umol/L of gefitinib. The inhibitory effects of gefitinib and/or celecoxib on cellular proliferation were tested by MTT assay. Cell cycle and apoptosis were analysed by flow cytometry. Western Blot was used to detect expression of COX-2, EGFR, phospho-EGFR, Akt and phospho-Akt, Erk, phosphor-Erk. Results:?Resistant index of PC9/G cells to gefitinib was about 147- to 198-fold higher than PC9 cells, and it was accompanied by tuclazepam significant increase of COX-2 expression in PC9/G cells. Inhibition of COX-2 with celecoxib in PC9/G resulted in dramatic inhibition of proliferation and promotion of apoptosis in response to gefitinib. PC9/G cells'sensitivity to gefitinib is restored. The combination of celecoxib and gefitinib significantly induced G0/G1 arrest. Furthermore, the combination as compared with effect of single agents showed strong reductions of p-AKT, p-ERK of PC9/G cell line. Conclusions:?These findings suggest that COX-2 signalling by PI3K/Akt and ERK pathway may be an important mechanism of acquired gefitinib resistance and may serve as an alternative therapeutic target for NSCLC unresponsive to EGFR TKIs. THIS STUDY WAS SUPPORTED BY THE WU JIEPING FOUNDATION OF CHINA. (GRANT NO: 320.6750.12211) YANG D1, ZHANG Y1, HONG Q1, HU J1, LI C1, PAN B2, WANG Q3, DING F1, SONG Y1, BAI C1 1Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, Shanghai, China, 2Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, Shanghai, China, 3Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, China Background and Objective:?In this Tenofovir study, we applied a combined cancer biomarker panel to help clinically identify small-cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) in a high-risk population. Methods:?Serum levels of four biomarkers (ProGRP, CEA, SCC and CYFRA21-1) were determined in 153 patients with a high-risk of lung cancer (12 with a new diagnosis of SCLC, 52 with NSCLC and 89 without lung cancer). The diagnosis delay information was collected by interviewing all the participants. Results:?We found significantly higher serum levels of ProGRP (p?
