{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T04:53:39Z","timestamp":1792212819266,"version":"4.4.0"},"reference-count":52,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2022,9,5]],"date-time":"2022-09-05T00:00:00Z","timestamp":1662336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The activity of drug transporters is central to the secretory function of the kidneys and a defining feature of renal proximal tubule epithelial cells (RPTECs). The expression, regulation, and function of these membrane-bound proteins is well understood under normal renal physiological conditions. However, the impact of drug transporters on the pathophysiology of kidney cancer is still elusive. In the present study, we employed different renal cell carcinoma (RCC) cell lines and a prototypical non-malignant RPTEC cell line to characterize the activity, expression, and potential regulatory mechanisms of relevant renal drug transporters in RCC in vitro. An analysis of the uptake and efflux activity, the expression of drug transporters, and the evaluation of cisplatin cytotoxicity under the effects of methylation or epidermal growth factor receptor (EGFR) inhibition showed that the RCC cells retained substantial drug transport activity. In RCC cells, P-glycoprotein was localized in the nucleus and its pharmacological inhibition enhanced cisplatin toxicity in non-malignant RPTECs. On the other hand, methylation inhibition enhanced cisplatin toxicity by upregulating the organic cation uptake activity in RCC cells. Differential effects of methylation and EGFR were observed in transporter expression, showing regulatory heterogeneity in these cells. Interestingly, the non-malignant RPTEC cell line that was used lacked the machinery responsible for organic cation transport, which reiterates the functional losses that renal cells undergo in vitro.<\/jats:p>","DOI":"10.3390\/ijms231710177","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T05:17:23Z","timestamp":1662441443000},"page":"10177","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["In Vitro Characterization of Renal Drug Transporter Activity in Kidney Cancer"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0861-0201","authenticated-orcid":false,"given":"Pedro","family":"Caetano-Pinto","sequence":"first","affiliation":[{"name":"Department of Urology, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathanil","family":"Justian","sequence":"additional","affiliation":[{"name":"Department of Urology, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Dib","sequence":"additional","affiliation":[{"name":"Department of Urology, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jana","family":"Fischer","sequence":"additional","affiliation":[{"name":"Department of Urology, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryna","family":"Somova","sequence":"additional","affiliation":[{"name":"Department of Urology, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Burchardt","sequence":"additional","affiliation":[{"name":"Department of Urology, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4197-6643","authenticated-orcid":false,"given":"Ingmar","family":"Wolff","sequence":"additional","affiliation":[{"name":"Department of Urology, University Medicine Greifswald, 17475 Greifswald, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Oswald, S., M\u00fcller, J., Neugebauer, U., Schr\u00f6ter, R., Herrmann, E., Pavenst\u00e4dt, H., and Ciarimboli, G. 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