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Page 42
Volume 2
Journal of Molecular Cancer
Cancer & Primary Healthcare 2019
May 20-21, 2019
Cancer Research & Oncology
Primary Healthcare and Medicare Summit
May 20-21, 2019 | Rome, Italy
25
th
Global Meet on
World Congress on
&
Ultra-low dose DPI is a cheap and effective potential therapeutic agent to prevent colitis-
associated colorectal cancer
Yue Kuai
Zhejiang University School of Medicine, China.
Background:
There are about 15-20% colorectal cancer developed from colitis. The most common forms of
inflammatory bowel disease are Crohn’s disease (CD) and ulcerative colitis (UC).The pathogenesis of UC
and CD is various and including immunologic, environmental and genetic factors.Excessive reactive oxygen
species (ROS) production has been observed in the inflamed mucosa of IBD patients. ROS is widely known as
a negative factor on cancer initiation,progression and survival stage. NADPH oxidases (NOXs) are the main
resource of ROS. Although diphenyleneiodonium (DPI) were assessed as inhibitors of both mitochondrial
respiration and ROS synthesis and used in research for decades, few research using it as an potential drug in
mice model.
Methods:
We used male C57BL/6 mice were treated with 3.5% DSS and 2% DSS respectively for five days and
seven days to make fatal enteritis and early stage colitis. After the DSS period, ultra-low dose DPI or control
solvent was intraperitoneal injection everyday. Then, the survival rate and inflammatory level of intestinal
tract in different groups were observed. Quantitative PCR and enzyme-linked immuno sorbent assay (ELISA)
were applied to evaluate the inflammatory factors between experimental and control groups. Intracellular ROS
were meatured by fuorescence microscopy using 2’7’-dichlorofluorescein diacetate(DCFH-DA). Htoxylin-
eosin (H&E) staining assessed histological patterns of several organs in DPI group and control group. Disease
activity index and histological activity index were assessed. Certain signal pathways were verified on protein
level.
Results:
In the fatal enteritis model, compared with control group, ultra-low dose DPI group has a better
survival rate. In early stage colitis model, mice’s weight and colon length are better than those in control group.
The level of inflammatory factors--COX2, IL6 ,TNF-a and IL12 are lower than the control group. In RAW246.7
cell line, compared with other concentrations, ultra-low dose DPI group had a lower level of inflammatory
factor, such as COX2, IL6, CCL5, IP10, TNF-a and MCP1.Utral-low dose DPI could inhibited NF-κB and
MAPK pathway. Histological patterns of DPI and control groups had no significant differences.
Conclusion:
Ultra-low dose DPI could prevent the progress of inflammatory bowl diseases and have no
negative effect on other organs.This study will provide a new pharmacological evidence that ultra-low dose
DPI has a positive significance for prevention of colitis-associated colorectal cancer.
kuaiyue@zju.edu.cnJ Mol Cancer, Volume 2