Gemcitabine-induced CXCL8 expression counteracts its actions by inducing tumor neovascularization

[email protected] with pancreatic ductal adenocarcinoma (PDAC) are frequently complicated with metastatic disease or locally advanced tumors, and consequently need chemotherapy. Gemcitabine is commonly used for PDAC treatment, but with limited efficacy. The capacity of gemcitabine to generate reactive oxygen species (ROS) in human pancreatic cancer cells, prompted us to examine its effects on the expression of pro-inflammatory cytokines and chemokines. We observed that gemcitabine enhanced selectively the expression of CXCL8 in human pancreatic cancer cells through ROS generation and NF-κB activation. In vitro blocking of CXCL8 failed to modulate gemcitabine-mediated inhibition of cell proliferation in human pancreatic cancer cells. Gemcitabine also enhanced CXCL8 expression in pancreatic cancer cells in xenografted tumor tissues. Moreover, anti-CXCL8 antibody treatment in vivo attenuated tumor formation as well as intra-tumoral vascularity in nude mice, which were transplanted with Miapaca-2 cells and treated with gemcitabine. Thus, gemcitabine-induced CXCL8 may counteract the drug through inducing neovascularization

ナイネンキカンシリンダナイガスリュウドウニカンスルジッケンテキケンキュウ

京都大学0048新制・論文博士工学博士乙第3829号論工博第1162号新制||工||435(附属図書館)5865UT51-54-H129(主査)教授 大東 俊一, 教授 池上 詢, 教授 赤松 映明学位規則第5条第2項該当Kyoto UniversityDA