{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T18:19:56Z","timestamp":1774117196893,"version":"3.50.1"},"reference-count":22,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:00:00Z","timestamp":1600300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Tumour drug resistance is one of the most urgent issues faced by anti\u2010tumour therapies. P\u2010glycoprotein (P\u2010gp) has been reported to be correlated with drug resistance. In this study, we aimed to study the synergistic effect of fluorouracil (5FU) and Ubenimex (UBE) on drug resistance in lung cancer. In this study, the tumour inhibitory role of 5FU and UBE was assessed in nude mice bearing A549 or A549\/ADR. Real\u2010time polymerase chain reaction, Western blot and immunohistochemical were performed to analyse the mRNA and protein expression of P\u2010gp. TUNEL assay was used to evaluate the apoptosis of A549\/ADR cells under 5FU and UBE treatment. MTT assay was performed to calculate the IC50 value of 5FU and UBE in A549 or A549\/ADR. Combined administration of 5FU and UBE significantly inhibited the tumour growth of multidrug\u2010resistant cell lines A549\/ADR in nude mice by down\u2010regulating the mRNA and protein expression of P\u2010gp. The apoptosis of A549\/ADR was remarkably elevated in nude mice treated with 5FU and UBE. The IC50 value of 5FU and UBE was dramatically declined in A549\/ADR cells compared with that of 5FU or UBE alone. Combined treatment of 5FU and UBE remarkably enhanced the apoptosis of A549\/ADR cells by enhancing the intracellular accumulation of the drugs. The results of this study demonstrated that UBE combined with fluorouracil attenuated multiple drug resistance and inhibited the expression of P\u2010gp in lung cancer.<\/jats:p>","DOI":"10.1111\/jcmm.15875","type":"journal-article","created":{"date-parts":[[2020,9,18]],"date-time":"2020-09-18T01:10:01Z","timestamp":1600391401000},"page":"12840-12847","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Inhibitory effect of Ubenimex combined with fluorouracil on multiple drug resistance and P\u2010glycoprotein expression level in non\u2010small lung cancer"],"prefix":"10.1111","volume":"24","author":[{"given":"Jun","family":"Wan","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Shenzhen People\u2019s Hospital The Second Clinical Medical College of Jinan University The First Affiliated Hospital of South University of Science and Technology  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xie\u2010an","family":"Ling","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Shenzhen People\u2019s Hospital The Second Clinical Medical College of Jinan University The First Affiliated Hospital of South University of Science and Technology  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Shenzhen People\u2019s Hospital The Second Clinical Medical College of Jinan University The First Affiliated Hospital of South University of Science and Technology  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guang\u2010gui","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery Shenzhen People\u2019s Hospital The Second Clinical Medical College of Jinan University The First Affiliated Hospital of South University of Science and Technology  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4536-5647","authenticated-orcid":false,"given":"Xi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Critical Care Medicine Shenzhen People\u2019s Hospital The Second Clinical Medical College of Jinan University The First Affiliated Hospital of South University of Science and Technology  Shenzhen China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,17]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.20107"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.athoracsur.2006.02.029"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.10.011"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(93)90431-U"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2012.01.007"},{"key":"e_1_2_9_7_1","first-page":"798","article-title":"Cellular uptake of 3H\u2010bestatin in tissues of mice after its intravenous injection","volume":"25","author":"Scornik OA","year":"1997","journal-title":"Drug Metab Dispos"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0215(20001015)88:2<274::AID-IJC20>3.0.CO;2-5"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3109\/02841869009093008"},{"key":"e_1_2_9_10_1","first-page":"1187","article-title":"Double blind controlled study of ubenimex (Bestatin) against squamous cell lung cancer\u2014a multicenter cooperative study","volume":"20","author":"Furuse K","year":"1993","journal-title":"Gan To Kagaku Ryoho"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1074"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V95.7.2378"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.12.7024"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2015.10.010"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2015.12.007"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1517\/17425255.4.2.205"},{"key":"e_1_2_9_17_1","first-page":"137","article-title":"Recent advances in the research of P\u2010glycoprotein inhibitors","volume":"2","author":"Yang K","year":"2008","journal-title":"Biosci Trends"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/15680266113136660159"},{"key":"e_1_2_9_19_1","first-page":"ed40","article-title":"Recycling existing drugs for cancer therapy: delivering low cost cancer care","volume":"8","author":"Pantziarka P","year":"2014","journal-title":"Ecancermedicalscience"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02967534"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/jps.22652"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)37730-5"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/80.1.14"}],"container-title":["Journal of Cellular and Molecular Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.15875","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jcmm.15875","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jcmm.15875","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,3]],"date-time":"2023-09-03T17:08:33Z","timestamp":1693760913000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jcmm.15875"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,17]]},"references-count":22,"journal-issue":{"issue":"21","published-print":{"date-parts":[[2020,11]]}},"alternative-id":["10.1111\/jcmm.15875"],"URL":"https:\/\/doi.org\/10.1111\/jcmm.15875","archive":["Portico"],"relation":{},"ISSN":["1582-1838","1582-4934"],"issn-type":[{"value":"1582-1838","type":"print"},{"value":"1582-4934","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,17]]},"assertion":[{"value":"2020-04-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-08-27","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-09-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}