title: Artesunate down-regulates immunosuppression from colorectal cancer Colon26 and RKO cells in vitro by decreasing transforming growth factor β1 and interleukin-10.
abstract: Immunosuppression is the main source of ineffective treatment on tumor, and the study aimed to investigate the effect of artesunate on tumor immunosuppression. Supernatants of re-cultivated murine colorectal cancer cell Colon26 and human colorectal cancer cell RKO after pre-treatment with or without artesunate were enrolled, and their effects on five immune parameters were assessed, including killing activity of natural killer (NK) and lymphocyte proliferation, as measured by MTT, and expressions of interleukin 2 receptor (IL-2R)α, CD3ε(+)ζ(+) and CD3ε(-)ζ(+) on lymphocytes, as analyzed by flow cytometry. Six immunosuppressive factors were measured by ELISA, including transforming growth factor (TGF) β1, vascular endothelial growth factor (VEGF), IL-4, IL-6, IL-10, and prostaglandin E2 (PGE2). Then, multiple linear regression analysis was applied to reveal the correlation between immunosuppression and immunosuppressive factors, and was used to confirm the findings. It was shown that Colon26 and RKO cells secreted immunosuppressive factors and inhibited these five immune parameters steadily. After pretreatment with artesunate, immunosuppression from the two cells was down-regulated significantly (all P<0.05), and the concentrations of TGF-β1 and IL-10 decreased greatly (all P<0.001). There were positive correlations between the down-regulation of immunosuppression and the decrease in TGF-β1 or IL-10. Their combined potency attributed to decreased TGF-β1 and IL-10 with respect to the down-regulating effect of artesunate on immunosuppression of NK killing, lymphocyte proliferation and expressions of IL-2Rα and CD3ε(+)ζ(+), was about 60%-90%. The present analysis provides clues that artesunate reverses the immunosuppression from Colon26 and RKO colorectal cancer cells by decreasing TGF-β1 and IL-10. This is probably one of the anti-tumor mechanisms of artesunate.
authors.affiliation: Department of Medical Technology, Bethune Military Medical College, Shijiazhuang 050081, China. Electronic address: cuicheng77777@sina.com.
authors.forename: Cheng
authors.initials: C
authors.lastname: Cui
authors.affiliation: Department of Orthopedics, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Helin
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Pathobiology and Immunology, Hebei University of Traditional Chinese Medicine, Shijiazhuang 050200, China.
authors.forename: Xinli
authors.initials: X
authors.lastname: Shi
authors.affiliation: Tumor Research Center, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Yazhuo
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Clinical Pharmacology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China.
authors.forename: Zhangying
authors.initials: Z
authors.lastname: Feng
authors.affiliation: Department of Medical Technology, Bethune Military Medical College, Shijiazhuang 050081, China.
authors.forename: Jingli
authors.initials: J
authors.lastname: Liu
authors.affiliation: Tumor Immunology and Gene Therapy Center, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Han
authors.affiliation: Department of Medical Technology, Bethune Military Medical College, Shijiazhuang 050081, China.
authors.forename: Junqiu
authors.initials: J
authors.lastname: Fu
authors.affiliation: Department of Medical Technology, Bethune Military Medical College, Shijiazhuang 050081, China.
authors.forename: Zhanjiang
authors.initials: Z
authors.lastname: Fu
authors.affiliation: Clinical Trial Centre, Mater Medical Research Institute, Queensland 4101, Australia.
authors.forename: Hui
authors.initials: H
authors.lastname: Tong
mesh_terms: D000818:Animals; D037621:Artemisinins / Q000494:pharmacology*; D000077332:Artesunate; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D006801:Humans; D007165:Immunosuppression Therapy; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*; D019139:Tumor Escape / Q000187:drug effects; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D037621:Artemisinins; D016207:Cytokines; D053773:Transforming Growth Factor beta1; D042461:Vascular Endothelial Growth Factor A; D016753:Interleukin-10; D000077332:Artesunate; D015232:Dinoprostone
keywords: Artesunate; Colon26; Colorectal cancer cells; Down-regulation; Immunosuppression; Immunosuppressive factors; RKO