{"doi":"10.3389/fonc.2020.00228","title":"Reversal Effect of ALK Inhibitor NVP-TAE684 on ABCG2-Overexpressing Cancer Cells","abstract":"Failure of cancer chemotherapy is mostly due to multidrug resistance (MDR). Overcoming MDR mediated by overexpression of ATP binding cassette (ABC) transporters in cancer cells remains a big challenge. In this study, we explore whether NVP-TAE684, a novel ALK inhibitor which has the potential to inhibit the function of ABC transport, could reverse ABC transporter-mediated MDR. MTT assay was carried out to determine cell viability and reversal effect of NVP-TAE684 in parental and drug resistant cells. Drug accumulation and efflux assay was performed to examine the effect of NVP-TAE684 on the cellular accumulation and efflux of chemotherapeutic drugs. The ATPase activity of ABCG2 transporter in the presence or absence of NVP-TAE684 was conducted to determine the impact of NVP-TAE684 on ATP hydrolysis. Western blot analysis and immunofluorescence assay were used to investigate protein molecules related to MDR. In addition, the interaction between NVP-TAE684 and ABCG2 transporter was investigated via in silico analysis. MTT assay showed that NVP-TAE684 significantly decreased MDR caused byABCG2-, but not ABCC1-transporter. Drug accumulation and efflux tests indicated that the effect of NVP-TAE684 in decreasing MDR was due to the inhibition of efflux function of ABCG2 transporter. However, NVP-TAE684 did not alter the expression or change the subcellular localization of ABCG2 protein. Furthermore, ATPase activity analysis indicated that NVP-TAE684 could stimulate ABCG2 ATPase activity. Molecular in silico analysis showed that NVP-TAE684 interacts with the substrate binding sites of the ABCG2 transporter. Taken together, our study indicates that NVP-TAE684 could reduce the resistance of MDR cells to chemotherapeutic agents, which provides a promising strategy to overcome MDR.","journal":"Frontiers in Oncology","year":2020,"id":97619,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":32,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9624,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":326821,"name":"Jing‐Quan Wang","orcid":"0000-0003-4331-0482","position":1,"is_corresponding":false},{"id":338479,"name":"Chao‐Yun Cai","orcid":null,"position":2,"is_corresponding":false},{"id":326824,"name":"Qingbin Cui","orcid":"0000-0003-2561-2962","position":3,"is_corresponding":false},{"id":334606,"name":"Yuqi Yang","orcid":"0000-0002-7830-8238","position":4,"is_corresponding":false},{"id":256746,"name":"Zhuo‐Xun Wu","orcid":null,"position":5,"is_corresponding":false},{"id":354699,"name":"Xing-Duo Dong","orcid":null,"position":6,"is_corresponding":false},{"id":326825,"name":"Leli Zeng","orcid":"0000-0002-3378-5241","position":7,"is_corresponding":false},{"id":483837,"name":"Linguo Zhao","orcid":null,"position":8,"is_corresponding":false},{"id":326827,"name":"Dong‐Hua Yang","orcid":"0000-0001-8649-5531","position":9,"is_corresponding":false},{"id":253755,"name":"Zhe‐Sheng Chen","orcid":"0000-0002-8289-097X","position":10,"is_corresponding":false},{"id":482779,"name":"Jingqiu Wang","orcid":"0000-0001-6636-3574","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-18T22:36:02.818637Z","pmid":"32175279","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}