Colorectal
adenocarcinoma is the most common type of
gastrointestinal cancer.
Colon adenocarcinoma is a major health problem worldwide due to the high prevalence and mortality rates associated with the disease. The majority of
colorectal carcinomas are
adenocarcinomas, which originate from the epithelial cells of the colorectal mucosa. HT-29 cells, which originate from human
colon adenocarcinoma, are used as an in vitro model to investigate the effect of malignant transformation on the expression of cellular constituents and functions of the intestinal epithelium.
Nitric oxide (NO) is a signaling molecule, which is involved in
inflammation and
carcinogenesis. It has been reported that enhanced inducible
NO synthase (iNOS) activity and the resulting NO concentrations in human colon
carcinoma contribute to
tumor progression and vascular invasion. The present study investigates the effect of pro-inflammatory
cytokine-induced
nitric oxide (NO) production and iNOS expression on the invasion of human colorectal
adenocarcinoma HT-29 cells, and the effect of extract from Cnidii Rhizoma on NO production and the invasiveness of HT-29 cells. Treatment of HT-29 cells with
cytokines, 100 U/ml
interferon γ, 10 ng/ml
interleukin-1 α and 25 ng/ml
tumor necrosis factor α was found to increase NO production. Pretreatment of the cells with Cnidii Rhizoma (0.1-5 mg/ml) resulted in an inhibition of
cytokine-induced NO production and iNOS expression. The invasiveness of HT-29 cells through
Matrigel was significantly increased by treatment with
cytokines. Cnidii Rhizoma inhibited the invasiveness of
cytokine-treated HT-29 cells through the
Matrigel-coated membrane in a concentration-dependent manner.
Matrix metalloproteinase (
MMP) activity in HT-29 cells increased following the treatment with
cytokines, and pretreatment of the cells with Cnidii Rhizoma inhibited
cytokine-induced MMP-2 activity. These results provide sufficient information for the further development of Cnidii Rhizoma as an antitumor metastatic agent for the treatment of
colon cancer.