SN38 increases IL-8 expression through the MAPK pathways in HCT8 cells

Zhang,Lei; Lou,Wen-Hui; Xu,Xue-Feng; Wu,Wenchuan; Rong,Ye-Fei; Jin,Da-Yong

doi:10.3892/ijmm.2016.2810

SN38 increases IL-8 expression through the MAPK pathways in HCT8 cells

Authors:
- Lei Zhang
- Wen-Hui Lou
- Xue-Feng Xu
- Wenchuan Wu
- Ye-Fei Rong
- Da-Yong Jin
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Affiliations: Pancreatic Cancer Group, General Surgery Department, Zhongshan Hospital, Fudan Universitiy, Shanghai 200232, P.R. China
Published online on: November 22, 2016 https://doi.org/10.3892/ijmm.2016.2810
Pages: 217-222

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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.

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