Advances in Clinical and Experimental Medicine

Title abbreviation: Adv Clin Exp Med
JCR Impact Factor (IF) – 1.736
5-Year Impact Factor – 2.135
Index Copernicus  – 168.52
MEiN – 70 pts

ISSN 1899–5276 (print)
ISSN 2451-2680 (online)
Periodicity – monthly

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Advances in Clinical and Experimental Medicine

2019, vol. 28, nr 10, October, p. 1285–1292

doi: 10.17219/acem/104543

Publication type: original article

Language: English

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Targeted blockade of interleukin 9 inhibits tumor growth in murine model of pancreatic cancer

Dongcheng Lu1,B,F, Qinyi Qin1,B,C, Ronge Lei1,C,E,F, Bangli Hu1,D,E, Shanyu Qin1,A,D,F

1 First Affiliated Hospital of Guangxi Medical University, Nanning, China

Abstract

Background. Interleukin 9 (IL-9) has been implicated in the pathogenesis of several tumor types, but the role of anti-IL-9 in pancreatic cancer remains unclear.
Objectives. We aimed to explore the mechanism and effects of blockading IL-9 in a pancreatic cancer mouse model.
Material and Methods. Panc02 cells were injected subcutaneously into mice to establish a mouse model. The mice were randomly categorized into 3 groups – the control group, the immunoglobulin G (IgG) group and the anti-IL-9 group – corresponding to intravenous tail injection of phosphate-buffered saline (PBS), IgG isotype antibody and anti-IL-9 antibody, respectively. Then, the expression of IL-9, interleukin-9 receptor (IL-9r), Janus kinase 1 (Jak1), Jak3, and signal transducer and activator of transcription 3 (Stat3) mRNA was tested with quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Interleukin 9 in the tumor tissue was detected using enzyme-linked immunosorbent assay (ELISA). Western blotting and immunocytochemistry were performed to detect STAT3 and phosphorylation signal transducers and activators of transcription-3 (pSTAT3). Matrix metalloproteinase 2 (MMP2), MMP9 and vascular endothelial growth factor (VEGF) levels were assessed using immunocytochemistry.
Results. Tumor weight in the anti-IL-9 group was significantly lower than in the other groups (p < 0.05). There was a remarkable survival benefit in the anti-IL-9 group compared to the other groups (p < 0.05). The concentration of IL-9 in tumor tissue was significantly downregulated in the anti-IL-9-treated mice (p < 0.05). The expression of Jak1 and Jak3 mRNA and pSTAT3, MMP2 and MMP9 proteins in the anti-IL-9 group was lower than that of the PBS or IgG groups (p < 0.05), but the STAT3 and VEGF protein levels showed no significant difference (p < 0.05).
Conclusion. Anti-IL-9 antibody could effectively restrain the growth of pancreatic cancer in mice, and this effect may partly occur by blocking the STAT3 pathway.

Key words

pancreatic cancer, JAK2/STAT3 pathway, IL-9 antibody

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