{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:13:27Z","timestamp":1790766807092,"version":"4.1.0"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T00:00:00Z","timestamp":1591920000000},"content-version":"vor","delay-in-days":163,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Xiangyang Central Hospital","award":["20160608"],"award-info":[{"award-number":["20160608"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioMed Research International"],"published-print":{"date-parts":[[2020,1]]},"abstract":"<jats:p>Renal cell carcinoma (RCC) is the most aggressive type of genitourinary cancer and is resistant to current therapies. Identifying drugs that enhance the efficacy of RCC standard\u2010of\u2010care drugs at sublethal concentrations is an alternative therapeutic strategy. Ribociclib is an orally available cyclin\u2010dependent kinase 4 and 6 (CDK4\/6) inhibitor that is approved for the treatment of breast cancer. In this work, we demonstrate that ribociclib at clinically achievable concentrations inhibits proliferation of 7 out of 9 tested RCC cell lines, with IC<jats:sub>50<\/jats:sub> range from 76 to 280\u2009nM. In addition, ribociclib induces apoptosis of RCC cells, but with less potency compared to its antiproliferative activity. The combination of ribociclib with chemotherapeutic or immunotherapeutic agents is synergistic in RCC cell lines. Of note, ribociclib demonstrates selective anti\u2010RCC activity by sparing normal kidney cells and fibroblast cells. Consistent with the <jats:italic>in vitro<\/jats:italic> findings, ribociclib inhibits RCC growth at the dosage that does not lead to toxicity in mice and enhances the <jats:italic>in vivo<\/jats:italic> efficacy of RCC standard\u2010of\u2010care drugs. Mechanistically, we show that ribociclib remarkably inhibits phosphorylation of retinoblastoma protein (Rb) at various sites, leading to the suppression of transcription of E2F target genes in RCC cells. Our findings clearly demonstrate the potency and selectivity of ribociclib in RCC preclinical models, via inhibition of the CDK4\/6\u2010cyclin D\/Rb pathway. Our findings support a clinical trial for the combination of ribociclib with chemo\/immunotherapy in RCC.<\/jats:p>","DOI":"10.1155\/2020\/9525207","type":"journal-article","created":{"date-parts":[[2020,6,12]],"date-time":"2020-06-12T23:33:58Z","timestamp":1592004838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Inhibition of the CDK4\/6\u2010Cyclin D\u2010Rb Pathway by Ribociclib Augments Chemotherapy and Immunotherapy in Renal Cell Carcinoma"],"prefix":"10.1155","volume":"2020","author":[{"given":"Dehong","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaosong","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuejun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3223-0954","authenticated-orcid":false,"given":"Jun","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,12]]},"reference":[{"key":"e_1_2_8_1_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2014.10.002"},{"key":"e_1_2_8_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2017.05.006"},{"key":"e_1_2_8_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneph.2017.82"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrdp.2017.9"},{"key":"e_1_2_8_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209615"},{"key":"e_1_2_8_6_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms18081776"},{"key":"e_1_2_8_7_2","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-14-0816"},{"key":"e_1_2_8_8_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(19990621)84:3<268::AID-IJC12>3.0.CO;2-8"},{"key":"e_1_2_8_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.urolonc.2014.05.006"},{"key":"e_1_2_8_10_2","doi-asserted-by":"publisher","DOI":"10.1186\/s12885-016-2775-2"},{"key":"e_1_2_8_11_2","doi-asserted-by":"crossref","unstructured":"AllisonS. 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