NS-398 enhances the efficacy of gemcitabine against lung adenocarcinoma through up-regulation of p21WAF1 and p27KIP1 protein.
Gemcitabine is a chemotherapeutic drug widely used in the treatment of non-small cell lung carcinoma, especially in advanced lung adenocarcinoma. However, many patients with advanced lung adenocarcinoma show a resistance to gemcitabine. Overexpression of COX-2 has been found in human non-small cell lung cancer tissues and itA s cell lines. Evidences show that COX-2 is involved in drug resistance of tumor. However, It is unknown whether COX-2 inhibitor can augment the efficacy of gemcitabine against lung adenocarcinoma. In this study, A549 cells were treated with gemcitabine and/or NS-398. The cell viability was examined by MTT assay. The cell cycle distribution and apoptotic ratio were tested by flow cytometry. The levels of p21WAF1, p27KIP1, p16INK4a and p15INK4b expression were detected by western blotting. After the cells were treated with gemcitabine along with NS-398, more cells were arrested in G1 phase and went to apoptosis. The levels of p21WAF1 and p27KIP1 protein were elevated, while the levels of p16INK4a and p15INK4b protein were not changed. It can be concluded that NS-398 enhances the efficacy of gemcitabine against lung adenocarcinoma and the efficacy is associated with up-regulation of p21WAF1 and p27KIP1protein.
Chen
X J
XJ
Department of Respiratory Disease, Qilu Hospital, Shandong University, Jinan, China.
Xiao
W
W
Qu
X
X
Zhou
S Y
SY
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism*; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004357:Drug Synergism; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009578:Nitrobenzenes / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D015854:Up-Regulation; D000093542:Gemcitabine
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; D003841:Deoxycytidine; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D050760:Cyclin-Dependent Kinase Inhibitor p27; D000093542:Gemcitabine