{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T14:23:44Z","timestamp":1781706224703,"version":"3.54.5"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T00:00:00Z","timestamp":1741305600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100004320","name":"Shiraz University of Medical Sciences","doi-asserted-by":"publisher","award":["28840"],"award-info":[{"award-number":["28840"]}],"id":[{"id":"10.13039\/501100004320","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Overcoming multidrug resistance (MDR), which is often caused by the overexpression of ATP binding cassette (ABC) transporters in cancer cells remains a major challenge for cancer treatment. Receptor tyrosine kinase inhibitors have demonstrated potential in reversing MDR. This study aimed to investigate the effects of c-MET RTKIs on the reversal of MDR induced by ABCG2 in breast cancer cells.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>MTT assay was employed to assess antiproliferative activity of c-MET inhibitors, including cabozantinib, crizotinib, and PHA665752. The accumulation of the fluorescent probe mitoxantrone was evaluated by flow cytometry. The drug\u2013drug interaction in combination treatments was analyzed using CalcuSyn software.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The combination of cabozantinib, crizotinib, and PHA665752 with mitoxantrone resulted in synergistic effects in MDR cells. This was demonstrated by the mean CI values of 0.32 \u00b1 0.07, 0.53 \u00b1 0.05, and 0.59 \u00b1 0.03, respectively. In the same cells, c-MET inhibitors enhanced the accumulation of mitoxantrone, with accumulation ratios ranging from 1.6 to 3.8, while no change was found in parental MCF-7 cells. Computational analysis revealed that the drug-binding region of ABCG2 transporters could be a viable target for these compounds.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>c-MET inhibitors hold potential as effective agents for reversing MDR in ABCG2-medicated drug-resistant cancer cells.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jpp\/rgaf008","type":"journal-article","created":{"date-parts":[[2025,3,7]],"date-time":"2025-03-07T17:54:51Z","timestamp":1741370091000},"page":"685-697","source":"Crossref","is-referenced-by-count":3,"title":["c-MET tyrosine kinase inhibitors reverse multidrug resistance in breast cancer cells by targeting ABCG2 transporter"],"prefix":"10.1093","volume":"77","author":[{"given":"Somayeh","family":"Nazari","sequence":"first","affiliation":[{"name":"Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences , Shiraz ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Mosaffa","sequence":"additional","affiliation":[{"name":"Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences , Mashhad ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Poustforoosh","sequence":"additional","affiliation":[{"name":"Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences , Shiraz ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano","family":"Saso","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology \u201cVittorio Erspamer\u201d, Sapienza University of Rome , P. le Aldo Moro 5, 00185 Rome ,","place":["Italy"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omidreza","family":"Firuzi","sequence":"additional","affiliation":[{"name":"Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences , Shiraz ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8078-1297","authenticated-orcid":false,"given":"Fatemeh","family":"Moosavi","sequence":"additional","affiliation":[{"name":"Medicinal and Natural Products Chemistry Research Center, Shiraz University of Medical Sciences , Shiraz ,","place":["Iran"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,7]]},"reference":[{"key":"2025050201523060500_CIT0001","doi-asserted-by":"publisher","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J Clin"},{"key":"2025050201523060500_CIT0002","doi-asserted-by":"publisher","first-page":"117486","DOI":"10.1016\/j.bmc.2023.117486","article-title":"The mechanisms of multidrug resistance of breast cancer and research progress on related reversal agents","volume":"95","author":"Yu","year":"2023","journal-title":"Bioorg Med Chem"},{"key":"2025050201523060500_CIT0003","doi-asserted-by":"publisher","first-page":"138","DOI":"10.1016\/j.ctrv.2018.08.009","article-title":"Evolution in sites of recurrence over time in breast cancer patients treated with adjuvant endocrine therapy","volume":"70","author":"Algorashi","year":"2018","journal-title":"Cancer Treat Rev"},{"key":"2025050201523060500_CIT0004","doi-asserted-by":"publisher","first-page":"1883","DOI":"10.1007\/s11033-021-06155-w","article-title":"ABC transporter superfamily. 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