期刊
CANCER BIOLOGY & THERAPY
卷 6, 期 7, 页码 1096-1100出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/cbt.6.7.4328
关键词
IL-6; pancreatic cancer; cytokine; Th2; VEGF; NRP-1; hypoxia
类别
资金
- NCCIH NIH HHS [R21 AT003094] Funding Source: Medline
- NCI NIH HHS [CA85822] Funding Source: Medline
- NHLBI NIH HHS [HL072716, HL065916, HL08347] Funding Source: Medline
- NIBIB NIH HHS [EB002436] Funding Source: Medline
- NIDCR NIH HHS [R01 DE15543] Funding Source: Medline
Background: Although upregulation of interleukin-6 (IL-6) is associated with many solid tumors, its role in pancreatic cancer has not been well elucidated. In this study, we examined the expression of IL-6 in pancreatic cancer cells, and determined the effect of exogenous IL-6 on cytokine secretion, gene expression and signaling in human pancreatic cancer cells. Methods: The mRNA levels of IL-6, VEGF(165), neuropilin-1 (NRP-1) and neuropilin-2 (NRP-2) were determined by real-time RT PCR. Phosphorylation of ERK2 in pancreatic cancer cells was determined by using Bio-Plex phosphoprotein assay. The expression of IL-6 and other cytokines in human pancreatic cancer cell lines was determined with Bio-Plex cytokine assay. Results: Pancreatic cancer cell lines expressed higher levels of IL-6 than normal human pancreatic ductal epithelium (HPDE) cells. Exogenous IL-6 increased the secretion of multiple Th2 type of cytokines in Panc-1, MIA PaCa-2 and BxPC-3 cells. IL-6 also upregulated the expression of VEGF(165), and NRP-1, and both IL-6 and VEGF165 were inducible by hypoxia. In addition, IL-6 activated ERK2 signaling pathways in pancreatic cancer cells. Conclusions: IL-6 may be involved in promoting human pancreatic cancer development by furnishing Th2 type of cytokine environment and upregulating cell proliferation and angiogenesis related genes. Targeting IL-6 might be an effective treatment for pancreatic cancer.
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