{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Liu Z"],"funding":["mylan chair endowment fund","metavivor","NIEHS NIH HHS","NCI NIH HHS","national institutes of health","national institute of general medical sciences","NIGMS NIH HHS","NIH HHS"],"pagination":["3575-3587"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9511176"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["95(11)"],"pubmed_abstract":["In our previous work, PC-9-Br, a PC-9 brain seeking line established via a preclinical animal model of lung cancer brain metastasis (LCBM), exhibited not only resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib in vitro, but also chemotherapy regimens of cisplatin plus etoposide in vivo. Using this cell line, we investigated novel potential targeted therapeutics for treating LCBM in vitro and in vivo to combat drug resistance. Significant increases in mRNA and protein expression levels of Bcl-2 were found in PC-9-Br compared with parental PC-9 (PC-9-P), but no significant changes of Bcl-XL were observed. A remarkable synergistic effect between EGFR-TKI gefitinib and Bcl-2 inhibitors ABT-263 (0.17 ± 0.010 µM at 48 h and 0.02 ± 0.004 µM at 72 h), or "],"journal":["Archives of toxicology"],"pubmed_title":["Overcoming the acquired resistance to gefitinib in lung cancer brain metastasis in vitro and in vivo."],"pmcid":["PMC9511176"],"funding_grant_id":["P20 GM121322","R15 ES026789","K00 CA253768","P20GM121322-03","R15ES026789","1008553R","U54 GM104942"],"pubmed_authors":["Saralkar P","Lockman PR","Liu Z","Shah N","Blethen KE","Mohammad A","Fladeland R","Gao W","Sprowls SA","Marshall KL","Arsiwala TA"],"additional_accession":[]},"is_claimable":false,"name":"Overcoming the acquired resistance to gefitinib in lung cancer brain metastasis in vitro and in vivo.","description":"In our previous work, PC-9-Br, a PC-9 brain seeking line established via a preclinical animal model of lung cancer brain metastasis (LCBM), exhibited not only resistance to epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) gefitinib in vitro, but also chemotherapy regimens of cisplatin plus etoposide in vivo. Using this cell line, we investigated novel potential targeted therapeutics for treating LCBM in vitro and in vivo to combat drug resistance. Significant increases in mRNA and protein expression levels of Bcl-2 were found in PC-9-Br compared with parental PC-9 (PC-9-P), but no significant changes of Bcl-XL were observed. A remarkable synergistic effect between EGFR-TKI gefitinib and Bcl-2 inhibitors ABT-263 (0.17 ± 0.010 µM at 48 h and 0.02 ± 0.004 µM at 72 h), or ","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Nov","modification":"2026-04-08T11:53:52.527Z","creation":"2024-10-14T22:56:12.789Z"},"accession":"S-EPMC9511176","cross_references":{"pubmed":["34455456"],"doi":["10.1007/s00204-021-03147-4"]}}