{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T10:14:44Z","timestamp":1790158484830,"version":"4.1.0"},"reference-count":19,"publisher":"National Academy of Sciences","issue":"9","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2009,3,3]]},"abstract":"<jats:p>Claudin-3 (CLDN3) is a tight junction protein that is overexpressed in 90% of ovarian tumors. Previous in vitro studies have indicated that CLDN3 overexpression promotes the migration, invasion, and survival of ovarian cancer cells. Here, we investigated the efficacy of lipidoid-formulated CLDN3 siRNA in 3 different ovarian cancer models. Intratumoral injection of lipidoid\/CLDN3 siRNA into OVCAR-3 xenografts resulted in dramatic silencing of CLDN3, significant reduction in cell proliferation, reduction in tumor growth, and a significant increase in the number of apoptotic cells. Intraperitoneal injection of lipidoid-formulated CLDN3 siRNA resulted in a substantial reduction in tumor burden in MISIIR\/TAg transgenic mice and mice bearing tumors derived from mouse ovarian surface epithelial cells. Ascites development was reduced in CLDN3 siRNA-treated mice, suggesting the treatment effectively suppressed metastasis. Toxicity was not observed after multiple i.p. injections. Importantly, treatment of mice with nonimmunostimulatory 2\u2032-OMe modified CLDN3 siRNA was as effective in suppressing tumor growth as unmodifed siRNA. These results suggest that lipidoid-formulated CLDN3 siRNA has potential as a therapeutic for ovarian cancer.<\/jats:p>","DOI":"10.1073\/pnas.0813348106","type":"journal-article","created":{"date-parts":[[2009,2,10]],"date-time":"2009-02-10T23:03:55Z","timestamp":1234307035000},"page":"3426-3430","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":110,"title":["Claudin-3 gene silencing with siRNA suppresses ovarian tumor growth and metastasis"],"prefix":"10.1073","volume":"106","author":[{"given":"Yu-Hung","family":"Huang","sequence":"first","affiliation":[{"name":"Lankenau Institute for Medical Research, 100 E Lancaster Avenue, Wynnewood, PA 19096-3450;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhua","family":"Bao","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research, 100 E Lancaster Avenue, Wynnewood, PA 19096-3450;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weidan","family":"Peng","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research, 100 E Lancaster Avenue, Wynnewood, PA 19096-3450;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Goldberg","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kevin","family":"Love","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Bumcrot","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals, Inc., 300 Third Street, Cambridge, MA 02142; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey","family":"Cole","sequence":"additional","affiliation":[{"name":"Alnylam Pharmaceuticals, Inc., 300 Third Street, Cambridge, MA 02142; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Langer","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research and"},{"name":"Chemical Engineering Department, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Rm E25-342, Cambridge, MA 02139-4307;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel G.","family":"Anderson","sequence":"additional","affiliation":[{"name":"David H. Koch Institute for Integrative Cancer Research and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet A.","family":"Sawicki","sequence":"additional","affiliation":[{"name":"Lankenau Institute for Medical Research, 100 E Lancaster Avenue, Wynnewood, PA 19096-3450;"},{"name":"Department of Dermatology and Cutaneous Biology and"},{"name":"Kimmel Cancer Center, Jefferson Medical School, Thomas Jefferson University, 233 S 10th Street, Philadelphia, PA 19107"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2009,3,3]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.3322\/CA.2007.0010"},{"key":"e_1_3_3_2_2","first-page":"6281","article-title":"Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer","volume":"60","author":"Hough CD","year":"2000","unstructured":"CD Hough, et al., Large-scale serial analysis of gene expression reveals genes differentially expressed in ovarian cancer. Cancer Res 60, 6281\u20136287 (2000).","journal-title":"Cancer Res"},{"key":"e_1_3_3_3_2","first-page":"2567","article-title":"Tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer but not in ovarian cystadenomas","volume":"9","author":"Rangel LBA","year":"2003","unstructured":"LBA Rangel, et al., Tight junction proteins claudin-3 and claudin-4 are frequently overexpressed in ovarian cancer but not in ovarian cystadenomas. 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Cancer Res 63, 1389\u20131397 (2003).","journal-title":"Cancer Res"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/21.4.585"},{"key":"e_1_3_3_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1402"},{"key":"e_1_3_3_10_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00072.2007"},{"key":"e_1_3_3_11_2","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-05-2782"},{"key":"e_1_3_3_12_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa052985"},{"key":"e_1_3_3_13_2","doi-asserted-by":"publisher","DOI":"10.1089\/hum.2007.179"},{"key":"e_1_3_3_14_2","first-page":"186","article-title":"The claudin gene family:expression in normal and neoplastic tissues","volume":"6","author":"Hewitt KJ","year":"2006","unstructured":"KJ Hewitt, R Agarwal, PJ Morin, The claudin gene family:expression in normal and neoplastic tissues. BCM Cancer 6, 186\u2013193 (2006).","journal-title":"BCM Cancer"},{"key":"e_1_3_3_15_2","first-page":"7878","article-title":"Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium","volume":"61","author":"Long H","year":"2001","unstructured":"H Long, CD Crean, WH Lee, OW Cummings, TG Gabig, Expression of Clostridium perfringens enterotoxin receptors claudin-3 and claudin-4 in prostate cancer epithelium. Cancer Res 61, 7878\u20137881 (2001).","journal-title":"Cancer Res"},{"key":"e_1_3_3_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)63721-2"},{"key":"e_1_3_3_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ygyno.2008.01.024"},{"key":"e_1_3_3_18_2","doi-asserted-by":"publisher","DOI":"10.1002\/pros.20576"},{"key":"e_1_3_3_19_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.gt.3302580"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0813348106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T18:16:34Z","timestamp":1649787394000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0813348106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,3,3]]},"references-count":19,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2009,3,3]]}},"alternative-id":["10.1073\/pnas.0813348106"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0813348106","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,3,3]]},"assertion":[{"value":"2008-09-24","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2009-03-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}