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

Journal Article · Fri Mar 06 04:00:00 EST 2015 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2015.01.112· OSTI ID:22458518

Song, Yao; Baba, Tomohisa ^[1]; Li, Ying-Yi ^[2]; Furukawa, Kaoru; Tanabe, Yamato ^[1]; Matsugo, Seiichi ^[3]; Sasaki, Soichiro ^[1]; Mukaida, Naofumi ^[1]

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1. Division of Molecular Bioregulation, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920-1192 (Japan)
2. Cancer Research Institute, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai (China)
3. School of Natural System Bioengineering Course, College of Science and Engineering, Kanazawa University, Kanazawa, Ishikawa (Japan)

Patients 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. - Highlights: • Gemcitabine induced CXCL8 expression in human pancreatic cancer cells. • CXCL8 expression required ROS generation and NF-κB activation. • CXCL8 did not affect in vitro proliferation of human pancreatic cancer cells. • CXCL8 in vivo counteracted gemcitabine by inducing neovascularization.

• OSTI ID: 22458518
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 2 Vol. 458; ISSN BBRCA9; ISSN 0006-291X
• Country of Publication: United States
• Language: English

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60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
ANTIBODIES
CARCINOMAS
CELL PROLIFERATION
CHEMOTHERAPY
CHROMATIN
DRUGS
ENZYMES
HUMAN POPULATIONS
IN VITRO
IN VIVO
INFLAMMATION
INHIBITION
LYMPHOKINES
METASTASES
MICE
OXYGEN
PANCREAS
PATIENTS