title: SN38 increases IL-8 expression through the MAPK pathways in HCT8 cells.
abstract: The overexpression of interleukin-8 (IL-8) is closely associated with poor tumor differentiation, metastasis and tumor progression. This study aimed to examine the effects and mechanisms of action of SN38 (a metabolite of the camptothecin derivative, CPT-11) on IL-8 expression in HCT8 cells, using ELISA, CCK-8 and western blot analysis. Among jatrorrhizine, evodiamine, 5-fluorouracil and SN38, SN38 was found to inhibit the proliferation of HCT8 cells in a dose-dependent manner, but to increase IL-8 secretion from HCT8 cells. Of the other agents, evodiamine was found to inhibit both IL-8 secretion and cell proliferation, and jatrorrhizine was found to increase IL-8 secretion without any obvious inhibitory effect on cell proliferation. Further experiments revealed that the increased activation of p38 mitogen-activated protein kinase (MAPK), extracellular signal-regulated kinase (ERK)1/2 and c-Jun N-terminal kinase (JNK) by SN38 contributed to the decreased cell proliferation and to the overexpression of IL-8 induced by SN38. Our results suggested that the MAPK pathways are activated by SN38, resulting in the upregulation of IL-8 expression and in the inhibition of cell proliferation in an IL-8-independent manner. Thus, the potential benefit of the use of a combination of camptothecin-11 with other chemical drugs with inhibitory effects on IL-8 expression, should be paid more attention in treating colon cancer.
authors.affiliation: Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan Universitiy, Shanghai 200232, P.R. China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan Universitiy, Shanghai 200232, P.R. China.
authors.forename: Wen-Hui
authors.initials: WH
authors.lastname: Lou
authors.affiliation: Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan Universitiy, Shanghai 200232, P.R. China.
authors.forename: Xue-Feng
authors.initials: XF
authors.lastname: Xu
authors.affiliation: Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan Universitiy, Shanghai 200232, P.R. China.
authors.forename: Wenchuan
authors.initials: W
authors.lastname: Wu
authors.affiliation: Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan Universitiy, Shanghai 200232, P.R. China.
authors.forename: Ye-Fei
authors.initials: YF
authors.lastname: Rong
authors.affiliation: Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan Universitiy, Shanghai 200232, P.R. China.
authors.forename: Da-Yong
authors.initials: DY
authors.lastname: Jin
mesh_terms: D001599:Berberine / Q000031:analogs & derivatives / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism*; D000077146:Irinotecan; D053614:Janus Kinase 2 / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D016209:Interleukin-8; D011799:Quinazolines; C055785:jatrorrhizine; D001599:Berberine; D000077146:Irinotecan; C049639:evodiamine; D053614:Janus Kinase 2; D005472:Fluorouracil; D002166:Camptothecin