{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T23:20:27Z","timestamp":1788045627227,"version":"build-2784847793"},"reference-count":35,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2013,6,19]],"date-time":"2013-06-19T00:00:00Z","timestamp":1371600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Stichopus japonicus acid mucopolysaccharide (SJAMP) is an important biologically active compound that can be extracted from the body wall of the sea cucumber. The present study investigated the anti-tumor and immunomodulatory effects of SJAMP in an experimental hepatocellular carcinoma (HCC) model in rats. Three doses of SJAMP (17.5 mg\/kg, 35 mg\/kg, and 70 mg\/kg administered 5 days\/week via oral gavage) were given to rats with diethylnitrosamine (DEN)-induced HCC. SJAMP treatment significantly inhibited DEN-induced HCC by reducing both the number and mean volume of nodules, decreasing serum a-fetoprotein (AFP) levels and proliferating cell nuclear antigen (PCNA) expression in liver, and increasing p21 expression. Furthermore, SJAMP decreased the serum levels of ALT, AST, GGT and TNF-\u03b1 and increased serum IL-2. SJAMP administration also improved indices of spleen and thymus function and improved both macrophage phagocytosis and NK cell-mediated tumoricidal activity. Moreover, CD3+ and CD4+ T lymphocyte levels recovered significantly and the CD4+\/CD8+ T cell ratio normalized in a dose-dependent manner. In conclusion, SJAMP effectively inhibited the growth of HCC through the stimulation of immune organs and tissue proliferation, leading to the enhancement of cellular immunity pathways in rats.<\/jats:p>","DOI":"10.3390\/molecules18067179","type":"journal-article","created":{"date-parts":[[2013,6,19]],"date-time":"2013-06-19T12:17:30Z","timestamp":1371644250000},"page":"7179-7193","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Immunomodulatory Effect of Stichopus japonicus Acid Mucopolysaccharide on Experimental Hepatocellular Carcinoma in Rats"],"prefix":"10.3390","volume":"18","author":[{"given":"Yang","family":"Song","sequence":"first","affiliation":[{"name":"Institute of Nutrition, Qingdao University Medical College, Qingdao 266021, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shou-Jie","family":"Jin","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Qingdao University Medical College, Qingdao 266021, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lian-Hua","family":"Cui","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Qingdao University Medical College, Qingdao 266021, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jun","family":"Ji","sequence":"additional","affiliation":[{"name":"The Affiliated Hospital of Qingdao University Medical College, Qingdao 266021, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fu-Guo","family":"Yang","sequence":"additional","affiliation":[{"name":"Institute of Nutrition, Qingdao University Medical College, Qingdao 266021, Shandong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2013,6,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4300","DOI":"10.3748\/wjg.14.4300","article-title":"Hepatocellular carcinoma: Epidemiology, Risk factors and pathogenesis","volume":"14","author":"Gomaa","year":"2008","journal-title":"World J. Gastroenterol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.canlet.2005.11.032","article-title":"Immunomodulation and antitumor activity of kappa-carrageenan oligosaccharides","volume":"243","author":"Yuan","year":"2006","journal-title":"Cancer Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.3390\/md9101761","article-title":"High-value components and bioactives from sea cucumbers for functional foods-a review","volume":"9","author":"Bordbar","year":"2011","journal-title":"Mar. Drugs"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1097\/MAJ.0b013e318182ee45","article-title":"The research progress of antitumorous effectiveness of Stichopus japonicus acid mucopolysaccharide in north of China","volume":"337","author":"Lu","year":"2009","journal-title":"Am. J. Med. Sci."},{"key":"ref_5","first-page":"27","article-title":"A new method for separation and purification of acidic mucopolysaccharide from stichopus japonicus","volume":"7","author":"Fan","year":"1982","journal-title":"Zhong Yao Tong Bao"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0008-6215(96)00258-3","article-title":"Structure of fucose branches in the glycosaminoglycan from the body wall of the sea cucumber stichopus japonicus","volume":"297","author":"Kariya","year":"1997","journal-title":"Carbohydr. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1097\/MAJ.0b013e3181c20d01","article-title":"The effects of Stichopus japonicus acid mucopolysaccharide on the apoptosis of the human hepatocellular carcinoma cell line HepG2","volume":"339","author":"Lu","year":"2010","journal-title":"Am. J. Med. Sci."},{"key":"ref_8","first-page":"25","article-title":"Studies on the purification of water-soluble holothurian glycosides from Apostichpus japonicus and their tumor suppressing activity","volume":"44","author":"Fan","year":"2009","journal-title":"Yao Xue Xue Bao"},{"key":"ref_9","first-page":"99","article-title":"Prediction of venous metastases, recurrence, and prognosis in hepatocellular carcinoma based on a uique immune response signature of the liver microenvironment","volume":"10","author":"Budhu","year":"2006","journal-title":"CancerCell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1016\/j.imbio.2005.07.004","article-title":"Analysis of host versus tumor interaction in cancer patients: Opposing role of transforming growth factor-beta1 and interleu-kin-6 in the development of in situ tumor immunity","volume":"210","author":"Tsai","year":"2005","journal-title":"Immunobiology"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"320","DOI":"10.4049\/jimmunol.181.1.320","article-title":"Autoreactive T cells escape clonal deletion in the thymus by a CD24-dependent pathway","volume":"181","author":"Carl","year":"2008","journal-title":"J. Immunol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"606","DOI":"10.1038\/nri1669","article-title":"Structure and function of the spleen","volume":"5","author":"Mebius","year":"2005","journal-title":"Nat. Rev. Immunol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3934","DOI":"10.1016\/j.biomaterials.2009.04.001","article-title":"The effect of Gd@C82(OH)22 nanoparticles on the release of Th1\/Th2 cytokines and induction of TNF-alpha mediated cellular immunity","volume":"30","author":"Liu","year":"2009","journal-title":"Biomaterials"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"48","DOI":"10.4161\/onci.1.1.18344","article-title":"Immunotherapy of Hepatocellular carcinoma: Unique challenges and clinical opportunities","volume":"1","author":"Pardee","year":"2012","journal-title":"Oncoimmunology"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1016\/j.cell.2010.01.025","article-title":"Immunity, inflammation, and cancer","volume":"140","author":"Grivennikov","year":"2010","journal-title":"Cell"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1016\/j.ccr.2009.08.021","article-title":"A lymphotoxin-driven pathway to Hepatocellular carcinoma","volume":"16","author":"Haybaeck","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0304-3835(01)00630-9","article-title":"Immunohistochemical analysis of pro-apoptotic Bid level in chronic hepatitis, hepatocellular carcinoma and liver metastases","volume":"172","author":"Chen","year":"2001","journal-title":"Cancer Lett."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1002\/hep.24433","article-title":"Saffron: A potential candidate for a novel anticancer drug against hepatocellular carcinoma","volume":"54","author":"Amin","year":"2011","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1126\/science.152.3718.83","article-title":"Liver carcinogenesis by diethylnitrosamine in the rat","volume":"152","author":"Rajewsky","year":"1966","journal-title":"Science"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.jtemb.2012.02.001","article-title":"Effect of two selenium sources on hepatocarcinogenesis and several angiogenic cytokines in diethylnitrosamine-induced hepatocarcinoma rats","volume":"26","author":"Liu","year":"2012","journal-title":"J. Trace. Elem. Med. Biol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1016\/j.lfs.2007.06.023","article-title":"Cell proliferation and hepatocarcinogenesis in rat initiated by diethynitrosamine and promoted by Phenobarbital: potential roles of early DNA damage and liver metallothionein expression","volume":"81","author":"Chakraborty","year":"2007","journal-title":"Life Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1093\/carcin\/23.5.885","article-title":"Reduction of hepatocarcinogenesis by ursodeoxycholic acid in rats","volume":"23","author":"Oyama","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1038\/369574a0","article-title":"The p21 inhibitor of cyclin-dependent kinases controls DNA replication by interaction with PCNA","volume":"369","author":"Waga","year":"1994","journal-title":"Nature"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"4370","DOI":"10.1182\/blood-2007-06-097014","article-title":"Macrophages contribute to the antitumor activity of the anti-CD30 antibody SGN-30","volume":"110","author":"Oflazoglu","year":"2007","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1691","DOI":"10.1007\/s00262-009-0680-0","article-title":"Anti-cancer activity and mechanistic features of a NK cell activating molecule","volume":"58","author":"Kim","year":"2009","journal-title":"Cancer Immunol. Immunother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1931","DOI":"10.1053\/j.gastro.2009.12.051","article-title":"Radiofrequency thermal ablation for hepatocellular carcinoma stimulates autologous NK-cell response","volume":"138","author":"Zerbini","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1159\/000078444","article-title":"Effects of fentanyl on natural killer cell activity and on resistance to tumor metastasis in rats.Dose and timing study","volume":"11","author":"Shavit","year":"2004","journal-title":"Neuroimmunomodulation"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.smim.2006.01.008","article-title":"Regulatory T cells and Toll-like receptors in tumor immunity","volume":"18","author":"Wang","year":"2006","journal-title":"Semin. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1084\/jem.190.5.617","article-title":"Distinct role of antigen-specific T helper type1 (Th1) and Th2 cells in tumor eradication in vivo","volume":"190","author":"Nishimura","year":"1999","journal-title":"J. Exp. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1016\/S0198-8859(02)00420-2","article-title":"NK cells become Ki-67+ in MLC and expend depending on the lack of ligand for KIR on stimulator cells in IL-2 supplemented MLC","volume":"63","author":"Grzywacz","year":"2002","journal-title":"Hum. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1016\/j.coph.2004.04.004","article-title":"Tumor necrosis factor-alpha in the pathogenesis and treatment of cancer","volume":"4","author":"Anderson","year":"2004","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.cytogfr.2004.11.001","article-title":"Tumor necrosis factor, cancer and anticancer therpy","volume":"16","author":"Mocellin","year":"2005","journal-title":"Cytokine Growth Factor Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4672","DOI":"10.3390\/molecules17044672","article-title":"Effect of paeonol on antioxidant and immune regulatory activity in Hepatocellular carcinoma rats","volume":"17","author":"Chen","year":"2012","journal-title":"Molecules"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1016\/S0039-6060(99)70206-0","article-title":"Antiangiogenic therapy of human esophageal cancers with thalidomide in nude mice","volume":"125","author":"Kotoh","year":"1999","journal-title":"Surgery"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.jep.2008.11.023","article-title":"Immunomodulatory effects of Abnormal Sava Munsiq, a traditional Uighur medicine, on the combined stress mice","volume":"122","author":"Amat","year":"2009","journal-title":"J. Ethnopharmacol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/18\/6\/7179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:47:26Z","timestamp":1760219246000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/18\/6\/7179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,6,19]]},"references-count":35,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2013,6]]}},"alternative-id":["molecules18067179"],"URL":"https:\/\/doi.org\/10.3390\/molecules18067179","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,6,19]]}}}