{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:57:47Z","timestamp":1787065067756,"version":"build-2736575974"},"reference-count":35,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T00:00:00Z","timestamp":1638316800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"JSPS KAKENHI","award":["19K16451 and 18K06793"],"award-info":[{"award-number":["19K16451 and 18K06793"]}]},{"name":"Nagai Memorial Research Scholarship","award":["N-181101"],"award-info":[{"award-number":["N-181101"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Epithelial\u2013mesenchymal transition (EMT) plays a role in cancer metastasis as well as in drug resistance through various mechanisms, including increased drug efflux mediated by P-glycoprotein (P-gp). In this study, we investigated the activation mechanism of P-gp, including its regulatory factors, during EMT in hepatoblastoma-derived HepG2 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>HepG2 cells were transfected with SNAI1 using human adenovirus serotype 5 vector. We quantified mRNA and protein expression levels using qRT-PCR and western blot analysis, respectively. P-gp activity was evaluated by uptake assay, and cell viability was assessed by an MTT assay.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key findings<\/jats:title>\n                    <jats:p>P-gp protein expression on plasma membrane was higher in SNAI1-transfected cells than in Mock cells, although there was no difference in P-gp protein level in whole cells. Among the scaffold proteins such as ezrin, radixin and moesin (ERM), only radixin was increased in SNAI1-transfected cells. Uptake of both Rho123 and paclitaxel was decreased in SNAI1-transfected cells, and this decrease was blocked by verapamil, a P-gp inhibitor. The reduced susceptibility of SNAI1-transfected cells to paclitaxel was reversed by elacridar, another P-gp inhibitor.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Increased expression of radixin during SNAI1-induced EMT leads to increased P-gp membrane expression in HepG2 cells, enhancing P-gp function and thereby increasing drug resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jpp\/rgab051","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T07:14:00Z","timestamp":1614928440000},"page":"1609-1616","source":"Crossref","is-referenced-by-count":6,"title":["Drug resistance via radixin-mediated increase of P-glycoprotein membrane expression during SNAI1-induced epithelial-mesenchymal transition in HepG2 cells"],"prefix":"10.1093","volume":"73","author":[{"given":"Hiroki","family":"Kamioka","sequence":"first","affiliation":[{"name":"Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare , Takasaki-shi, Gunma ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazue","family":"Edaki","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmaceutics, Faculty of Pharmacy, Takasaki University of Health and Welfare , Takasaki-shi, Gunma ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haruka","family":"Kasahara","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmaceutics, Faculty of Pharmacy, Takasaki University of Health and Welfare , Takasaki-shi, Gunma ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takumi","family":"Tomono","sequence":"additional","affiliation":[{"name":"Laboratory of Clinical Pharmacokinetics, Graduate School of Pharmaceutical Sciences, Takasaki University of Health and Welfare , Takasaki-shi, Gunma ,","place":["Japan"]},{"name":"Laboratory of Drug Delivery System, Faculty of Pharmaceutical Sciences, Setsunan University , Hirakata-shi, Osaka ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kentaro","family":"Yano","sequence":"additional","affiliation":[{"name":"Laboratory of Biopharmaceutics, Faculty of Pharmacy, Takasaki University of Health and Welfare , Takasaki-shi, Gunma ,","place":["Japan"]},{"name":"Laboratory of Drug Metabolism and Pharmacokinetics, Yokohama University of Pharmacy , Yokohama, Kanagawa 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