title: Shikonin derivatives protect immune organs from damage and promote immune responses in vivo in tumour-bearing mice.
abstract: Shikonin, a major component of Lithospermum erythrorhizon and Arnebia euchroma, exhibits antiinflammatory, immunomodulatory and antitumour activities. Although many recent studies have focused on the antitumour effects of shikonin, the exact mechanisms underlying its antitumour and immunomodulatory effects in tumour-bearing mice remain unclear. The aim of the present study was to investigate the antitumour and immunomodulatory effects of shikonin derivatives (ShD) in tumour-bearing mice. Swiss mice inoculated with hepatoma HepA(22) or sarcoma 180 (S(180)) cells were treated with ShD or 5-fluorouracil (5Fu). Survival time, immune organs, natural killer cell activity, lymphocytes, lymphocyte transformation and interleukin (IL)-2 production were analysed. ShD significantly prolonged the survival (median survival time prolonged by >7 days) of tumour-bearing mice in a dose-dependent manner, inhibited the growth of transplantable neoplasms (inhibitory rate, > 33%), and recovered (at [ShD] = 2.5 mg/kg/day) or increased (at [ShD] > 5 mg/kg/day) the number of CD3- and CD19-positive cells. ShD also played a role in protecting the immune organs from damage and reversed or enhanced immune responses, as noted by the nearly normal thymic structure; enlarged splenic corpuscles; and improved natural killer cell activity, lymphocyte transformation and IL-2 production in ShD-treated mice. ShD reduced the tumour load of tumour-bearing mice and protected the immune organs against tumour-induced damage and immune function impairment.
authors.affiliation: Department of Laboratory Medicine, the First Clinical College, Jilin University, Changchun 130021, China.
authors.forename: Su
authors.initials: S
authors.lastname: Long
authors.forename: Yan
authors.initials: Y
authors.lastname: GuangZhi
authors.forename: Guan
authors.initials: G
authors.lastname: BaoJie
authors.forename: Xu
authors.initials: X
authors.lastname: Wei
authors.forename: Hao
authors.initials: H
authors.lastname: YanYong
authors.forename: Wang
authors.initials: W
authors.lastname: YingLi
authors.forename: Zhang
authors.initials: Z
authors.lastname: Yang
authors.forename: Liu
authors.initials: L
authors.lastname: LiHua
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D028082:Boraginaceae / Q000737:chemistry*; D017252:CD3 Complex / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000276:immunology; D004305:Dose-Response Relationship, Drug; D005472:Fluorouracil; D007376:Interleukin-2 / Q000096:biosynthesis; D007694:Killer Cells, Natural / Q000187:drug effects; D029684:Lithospermum / Q000737:chemistry; D008113:Liver Neoplasms / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000187:drug effects; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology / Q000627:therapeutic use*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D012509:Sarcoma / Q000188:drug therapy* / Q000276:immunology; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013950:Thymus Gland / Q000187:drug effects
chemical_list: D000276:Adjuvants, Immunologic; D018941:Antigens, CD19; D000972:Antineoplastic Agents, Phytogenic; D017252:CD3 Complex; D007376:Interleukin-2; D009285:Naphthoquinones; D010936:Plant Extracts; C016101:shikonin; D005472:Fluorouracil