Targeted blockade of interleukin 9 inhibits tumor growth in murine model of pancreatic cancer
| Autor: | Dongcheng Lu, Bang-li Hu, Qinyi Qin, Ronge Lei, Shanyu Qin |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
STAT3 Transcription Factor
Vascular Endothelial Growth Factor A Immunocytochemistry Medicine (miscellaneous) General Biochemistry Genetics and Molecular Biology Immunoglobulin G chemistry.chemical_compound Mice Random Allocation Pancreatic cancer Internal Medicine medicine Animals Pharmacology (medical) Interleukin 9 STAT3 Genetics (clinical) biology Janus kinase 1 Interleukin-9 medicine.disease Molecular biology Vascular endothelial growth factor Pancreatic Neoplasms Disease Models Animal chemistry Reviews and References (medical) biology.protein Matrix Metalloproteinase 2 Antibody |
| Zdroj: | Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 28(10) |
| ISSN: | 1899-5276 |
| Popis: | 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). CONCLUSIONS 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. |
| Databáze: | OpenAIRE |
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