{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T07:58:37Z","timestamp":1785571117024,"version":"3.56.0"},"reference-count":25,"publisher":"SAGE Publications","issue":"7","license":[{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T00:00:00Z","timestamp":1782864000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"name":"Science and Technology Program of Jiangxi Provincial Health Commission","award":["202311851"],"award-info":[{"award-number":["202311851"]}]},{"name":"the joint project of \"Science and Technology + National Regional Medical Center\" in Ganzhou city in 2022","award":["2022-YB1447"],"award-info":[{"award-number":["2022-YB1447"]}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Int Med Res"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate whether naringin enhances the chemosensitivity of nasopharyngeal carcinoma\u2013derived CNE2 cells to paclitaxel and identify potential molecular mediators.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CNE2 cells were treated with naringin alone or in combination with paclitaxel, cisplatin, or 5-fluorouracil. Cell viability, proliferation, and migration were assessed using cell counting kit-8 and Transwell assays. Transcriptomic profiling followed by bioinformatic analysis of Gene Expression Omnibus datasets (GSE53819, GSE12452, and GSE102349) was performed to identify nasopharyngeal carcinoma prognosis\u2013related genes.\n                      <jats:italic toggle=\"yes\">AKR1C3<\/jats:italic>\n                      overexpression was established via lentiviral transduction, and pharmacological inhibition was performed using ASP9521. mRNA and protein expression were validated using reverse transcription quantitative polymerase chain reaction and Western blot analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Naringin (160\u2005\u03bcM) demonstrated a trend toward reducing the half-maximal inhibitory concentration of paclitaxel from 10.52 to 8.04\u2005nM; however, it did not significantly alter sensitivity to cisplatin or 5-fluorouracil. Combined treatment with 2\u2005nM paclitaxel and 160\u2005\u03bcM naringin synergistically suppressed CNE2 proliferation and migration compared with that using either agent alone (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.05). Bioinformatic analysis revealed that high\n                      <jats:italic toggle=\"yes\">AKR1C3<\/jats:italic>\n                      expression was correlated with improved survival in patients with nasopharyngeal carcinoma (\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      \u2009&lt;\u20090.05), whereas high\n                      <jats:italic toggle=\"yes\">PAIP1<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">PRKDC<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">PTPRR<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">COL12A1<\/jats:italic>\n                      expressions were correlated with poorer outcomes. Reverse transcription quantitative polymerase chain reaction confirmed that both naringin and paclitaxel upregulated\n                      <jats:italic toggle=\"yes\">AKR1C3<\/jats:italic>\n                      mRNA, with the combination producing the strongest effect. Gain-of-function studies demonstrated that\n                      <jats:italic toggle=\"yes\">AKR1C3<\/jats:italic>\n                      overexpression significantly enhanced paclitaxel sensitivity, with half-maximal inhibitory concentration values decreasing from 13.63 to 6.994\u2005nM in CNE2 cells and from 8.534 to 4.668\u2005nM in CNE1 cells. Furthermore, the specific\n                      <jats:italic toggle=\"yes\">AKR1C3<\/jats:italic>\n                      inhibitor, ASP9521, significantly attenuated the synergistic anti-proliferative and anti-migratory effects of paclitaxel + naringin in CNE2 cells, confirming that naringin enhances chemosensitivity to paclitaxel by upregulating AKR1C3 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Naringin sensitizes CNE2 cells to paclitaxel, potentially via\n                      <jats:italic toggle=\"yes\">AKR1C3<\/jats:italic>\n                      upregulation. This flavonoid may represent a low-toxicity adjunct to enhance the efficacy of paclitaxel in nasopharyngeal carcinoma.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/03000605261470618","type":"journal-article","created":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T13:25:21Z","timestamp":1785331521000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Naringin sensitizes nasopharyngeal carcinoma cells to paclitaxel by inducing\n                    <i>AKR1C3<\/i>\n                    expression"],"prefix":"10.1177","volume":"54","author":[{"given":"Zhenhe","family":"Huang","sequence":"first","affiliation":[{"name":"Ganzhou People's Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3116-7792","authenticated-orcid":false,"given":"Yumei","family":"Qiu","sequence":"additional","affiliation":[{"name":"Ganzhou People's Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangchu","family":"Liu","sequence":"additional","affiliation":[{"name":"Ganzhou People's Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoli","family":"Chen","sequence":"additional","affiliation":[{"name":"Ganzhou People's Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4337-1974","authenticated-orcid":false,"given":"Xintao","family":"Wang","sequence":"additional","affiliation":[{"name":"Ganzhou People's Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,7,29]]},"reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)30956-0"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2016.08.006"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-17-2656"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/cac2.12218"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1124\/pharmrev.120.000122"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2022.823491"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2016.1236373"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.colsurfb.2017.11.068"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2018.03.051"},{"key":"e_1_3_2_11_2","doi-asserted-by":"crossref","unstructured":"Elsawy H Algefare AI Alfwuaires M et al. 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