title: Camptothecin and cisplatin upregulate ABCG2 and MRP2 expression by activating the ATM/NF-κB pathway in lung cancer cells.
abstract: Multidrug resistance (MDR) formation is an important problem in lung cancer chemotherapy. Our study showed that both camptothecin and cisplatin could not only induce ATM and NF-κB activation but also upregulate expression of the MDR-related genes ABCG2, MRP2 in NCI-H446 cells. Moreover, camptothecin and cisplatin-induced ABCG2 and MRP2 upregulation could be impaired by ATM and NF-κB inhibitors, indicating a relationship between ATM, NF-κB activation and MDR formation in lung cancer chemo-therapy. Our study indicates that ATM may serve as a potential molecular target for MDR formation in lung cancer chemotherapy.
authors: Department of Immunology, Basic Medicine Science, Medical College, Xiamen University, Xiamen 361005, P.R. China.
authors: Shi Zhong
authors: SZ
authors: Ke
authors: Xiao Yan
authors: XY
authors: Ni
authors: Yue Hua
authors: YH
authors: Zhang
authors: Yi Nan
authors: YN
authors: Wang
authors: Bin
authors: B
authors: Wu
authors: Feng Guang
authors: FG
authors: Gao
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis; D064007:Ataxia Telangiectasia Mutated Proteins; D002166:Camptothecin / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000970:Antineoplastic Agents; D064007:Ataxia Telangiectasia Mutated Proteins; D002166:Camptothecin; D018797:Cell Cycle Proteins; D002945:Cisplatin; D004268:DNA-Binding Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D017346:Protein Serine-Threonine Kinases; D019253:Proto-Oncogene Proteins c-bcl-2; D025521:Tumor Suppressor Proteins; C000715087:ABCC2 protein, human; C116614:ABCG2 protein, human; C576324:ATM protein, human